vasoactive-intestinal-peptide and Alzheimer-Disease

A hallmark in most neurological disorders is a massive neuronal cell death, in which uncontrolled immune response is usually involved, leading to neurodegeneration. The vasoactive intestinal peptide (VIP) is a pleiotropic peptide that combines neuroprotective and immunomodulatory actions. Alterations on VIP/VIP receptors in patients with neurodenegerative diseases, together with its involvement in the development of embryonic nervous tissue, and findings found in VIP-deficient mutant mice, have showed the relevance of this endogenous peptide in normal physiology and in pathologic states of the central nervous system (CNS). In this review, we will summarize the role of VIP in normal CNS and in neurological disorders. The studies carried out with this peptide have demonstrated its therapeutic effect and render it as an attractive candidate to be considered in several neurological disorders linked to neuroinflammation or abnormal neural development.

Topics: Alzheimer Disease; Animals; Autistic Disorder; Brain; Brain Injuries; Developmental Disabilities; Down Syndrome; Encephalitis; Female; Fetal Alcohol Spectrum Disorders; Humans; Mice; Multiple Sclerosis; Nervous System Diseases; Neuroprotective Agents; Parkinson Disease; Pregnancy; Receptors, Vasoactive Intestinal Peptide; Vasoactive Intestinal Peptide

A rapid increase in incidence of neurodegenerative disorders has been observed with the aging of the population. Alzheimer's disease (AD) is the most common neurodegenerative disorder among the elderly. It is characterized by memory dysfunction, loss of lexical access, spatial and temporal disorientation and impairment of judgement clinically. Unfortunately, clinical development of drugs for the symptomatic and disease-modifying treatment of AD has resulted in both promise and disappointment. Indeed, a large number of drugs with differing targets and mechanisms of action were investigated with only a few of them being clinically available. The targeted drug delivery to the central nervous system (CNS), for the diagnosis and treatment of neurodegenerative disorders such as AD, is restricted due to the limitations posed by the blood-brain barrier (BBB) as well as due to opsonization by plasma proteins in the systemic circulation and peripheral side-effects. Over the last decade, nanoparticle-mediated drug delivery represents one promising strategy to successfully increase the CNS penetration of several therapeutic moieties. Different nanocarriers are being investigated to treat and diagnose AD by delivering at a constant rate a host of therapeutics over times extending up to days, weeks or even months. This review provides a concise incursion on the current pharmacotherapies for AD besides reviewing and discussing the literature on the different drug molecules that have been successfully encapsulated in nanoparticles (NPs). Some of them have been shown to cross the BBB and have been tested either for diagnosis or treatment of AD. Finally, the route of NPs administration and the future prospects will be discussed.

Topics: Alzheimer Disease; Amyloid; Animals; Blood-Brain Barrier; Chelating Agents; Cholinesterase Inhibitors; Drug Delivery Systems; Flavonoids; Hormones; Humans; Nanoparticles; Phenols; Polyphenols; Vasoactive Intestinal Peptide

Topics: Administration, Intranasal; Alzheimer Disease; Animals; Cell Death; Humans; In Vitro Techniques; Learning; Memory; Neurons; Neuropeptides; Rats; Vasoactive Intestinal Peptide

To understand and intervene in neuronal cell death, intensive investigations have been directed at the discovery of intracellular and extracellular factors that provide natural neuroprotection. This goal has fundamental importance for both rational strategies for the treatment of neurodegenerative diseases and also the delineation of molecular mechanisms that regulate nervous system differentiation and growth. We have discovered a potential interface among these fields of research with activity-dependent neurotrophic factor (ADNF), a protein containing sequence homologies to intracellular stress proteins that is found in the extracellular milieu of astroglial cells incubated with the neuropeptide vasoactive intestinal peptide (VIP). Femtomolar concentrations of ADNF and a short peptide sequence derived from it (a peptidergic active site) protected neurons from death associated with a broad range of toxins, including those related to Alzheimer's disease, the human immunodeficiency virus, excito-toxicity, and electrical blockade. Because the activity of the protein was mimicked by a short peptide fragment, this peptide is now proposed as a lead compound for drug development against neurodegeneration.

Topics: Alzheimer Disease; Amino Acid Sequence; Animals; Cell Death; Heat-Shock Proteins; HIV; Humans; Nerve Growth Factors; Nerve Tissue Proteins; Neurons; Neurotoxins; Sequence Homology, Amino Acid; Vasoactive Intestinal Peptide

Topics: Alzheimer Disease; Basal Ganglia; Brain; Brain Chemistry; Cerebral Cortex; Choline O-Acetyltransferase; Enkephalin, Methionine; FMRFamide; gamma-Aminobutyric Acid; Glutamate Decarboxylase; Humans; Huntington Disease; Nerve Tissue Proteins; Neurofibrils; Neuropeptide Y; Neurotensin; Oligopeptides; Peptides; Substance P; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

The anatomic distribution of classical neurotransmitters, i.e. NA, DA, 5HT, ACH and GABA in the post-mortem autopsied brain of Alzheimer's disease (AD) has been reviewed. In addition, the results and reviews reported in this paper give evidence for the change of a large number of neuropeptides in AD on the basis of immunohistochemical criteria. Among numerous peptidergic systems, abnormalities in SP, SS, NT and VIP have been observed. Therefore, no changes in the concentrations of CCK and TRH were reported. In this study, using immunohistochemical methods for SS changes in post-mortem brain material of three cases of AD and two controls, the following changes were observed: An important reduction of the SS-positive cell bodies and fibres in the cortex, the hippocampus, parahippocampic cortex, and neocortex, particularly in the parietal and frontal areas, as well as a reduction of SS cell bodies and fibres in the sub-cortical white matter. An amorphous SS-positive material in or close to the corona of a number of senile plaques. An important decrease of SS fibres and cell bodies in the lateral septi nuclei. An increase of the number and immunoreactive intensity of SS-positive fibres in the substantia innominata. In animal studies, an interaction between SS- and ACH turnover in the substantia innominata is reported. The GABA decrease as well as the SS deficit in the cortex area and sub-cortical white matter may lead to the interaction between SS and other neurotransmitters in AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain Chemistry; Cholecystokinin; Choline O-Acetyltransferase; Humans; Middle Aged; Neuropeptide Y; Neuropeptides; Somatostatin; Substance P; Vasoactive Intestinal Peptide

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Atrophy; Brain; Female; Mice; Neuroprotective Agents; Vasoactive Intestinal Peptide

The suprachiasmatic nucleus (SCN) of the hypothalamus, the master mammalian circadian pacemaker, synchronizes endogenous rhythms with the external day-night cycle. Older humans, particularly those with Alzheimer disease (AD), often have difficulty maintaining normal circadian rhythms compared to younger adults, but the basis of this change is unknown. We report that the circadian rhythm amplitude of motor activity in both AD subjects and age-matched controls is correlated with the number of vasoactive intestinal peptide-expressing SCN neurons. AD was additionally associated with delayed circadian phase compared to cognitively healthy subjects, suggesting distinct pathologies and strategies for treating aging- and AD-related circadian disturbances.

Topics: Actigraphy; Aged; Aged, 80 and over; Alzheimer Disease; Case-Control Studies; Cell Count; Circadian Rhythm; Female; Humans; Male; Middle Aged; Motor Activity; Neurons; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide

A major determinant in the pathogenesis of Alzheimer's disease (AD) is the deposition of beta-amyloid (Abeta) peptides in specific areas of the central nervous system. Therefore, animal models of Alzheimer amyloidosis are excellent tools to identify candidates to facilitate drug screening and to understand the molecular pathology of AD. Activity-dependent neuroprotective protein (ADNP) plays an essential role in brain development, and NAP (NAPVSIPQ, generic name: davunetide)--a peptide derived from ADNP--is currently in clinical development for the treatment of neurodegenerative disorders. However, the link between ADNP expression and AD remains unexplored. To test whether ADNP is affected by the onset of AD and progression, we employed the PS1xAPP mouse model (PS1(M146L) x APP(751SL) transgenic mice) to analyze the mRNA expression of ADNP in the hippocampus and cerebellum in early and advanced stages of disease. Results showed that ADNP expression in 6-month-old PS1xAPP mice hippocampus was higher than in wild-type (WT) mice. ADNP was originally identified as a vasoactive intestinal peptide (VIP)-responsive gene taking part in the VIP-mediated neurotrophic pathway. Interestingly, the expression of VIP was not affected in the same experimental setting, suggesting that ADNP expression is a VIP-independent marker associated with AD. Moreover, in the cerebellum, a brain area not affected by Abeta deposition, ADNP mRNA expression in 6-month-old PS1xAPP and WT were not different. A similar extent of hippocampal ADNP expression was observed in 18-month-old WT and PS1xAPP mice, in contrast to the differential expression level at 6 months of age. However, hippocampal ADNP expression in both WT and PS1xAPP was increased with aging similar to VIP mRNA expression. Our findings support the hypothesis that ADNP expression is related to early or mild AD progression by a VIP-independent mechanism.

Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Disease Models, Animal; Hippocampus; Homeodomain Proteins; Humans; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Tissue Proteins; Presenilin-1; Vasoactive Intestinal Peptide

Circadian disturbances, including a fragmented sleep-wake pattern and sundowning, are commonly reported early in the progression of Alzheimer's disease (AD). These changes are distinctly different from those observed in non-pathological aging. Transgenic models of AD are a promising tool in understanding the underlying mechanisms and cause of disease. A novel triple-transgenic model of AD, 3xTg-AD, is the only model to exhibit both Abeta and tau pathology, and mimic human AD. The present study characterized changes pertaining to circadian rhythmicity that occur prior to and post-AD pathology. Both male and female 3xTg-AD mice demonstrated alterations to their circadian pacemaker with decreased nocturnal behavior when compared to controls. Specifically, males showed greater locomotor activity during the day and shorter freerunning periods prior to the onset of AD-pathology, and females had a decrease in activity levels during their typical active phase. Both sexes did not differ in terms of their freerunning periods or photic phase shifting ability. A decrease in vasoactive intestinal polypeptide-containing and vasopressin-containing cells was observed in the suprachiasmatic nucleus of 3xTg-AD mice relative to controls. This study demonstrates that abnormalities in circadian rhythmicity in 3xTg-AD mice precede expected AD pathology. This suggests that human studies may wish to determine if similar circadian dysfunction is predictive of early-onset AD.

Topics: Age Factors; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Analysis of Variance; Animals; Animals, Genetically Modified; Chronobiology Disorders; Disease Models, Animal; Female; Gene Expression Regulation; Humans; Male; Mice; Mice, Inbred C57BL; Motor Activity; Nerve Growth Factors; Presenilin-1; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide; Vasopressins

The pineal hormone melatonin is involved in the regulation of circadian rhythms and feeds back to the central biological clock, the hypothalamic suprachiasmatic nucleus (SCN) via melatonin receptors. Supplementary melatonin is considered to be a potential treatment for aging and Alzheimer's disease (AD)-related circadian disorders. Here we investigated by immunocytochemistry the alterations of the MT1 melatonin receptor, the neuropeptides vasopressin (AVP) and vasoactive intestinal peptide (VIP) in the SCN during aging and AD. We found that the number and density of AVP/VIP-expressing neurons in the SCN did not change, but the number and density of MT1-expressing neurons in the SCN were decreased in aged controls compared to young controls. Furthermore, both MT1-expressing neurons and AVP/VIP-expressing neurons were strongly diminished in the last neuropathological stages of AD (Braak stages V-VI), but not in the earliest stages (Braak stages I-II), compared to aged controls (Braak stage 0). Our study suggests that the MT1-mediated effects of melatonin on the SCN are disturbed during aging and even more so in late stage AD, which may contribute to the clinical circadian disorders and to the efficacy of therapeutic melatonin administration under these conditions.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Aging; Alzheimer Disease; Female; Gene Expression Regulation; Humans; Male; Middle Aged; Neurons; Postmortem Changes; Receptor, Melatonin, MT1; Statistics, Nonparametric; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide; Vasopressins

Stearyl-Nle17-VIP (SNV) is a novel agonist of vasoactive intestinal peptide (VIP) exhibiting a 100-fold greater potency than the parent molecule and specificity for a receptor associated with neuronal survival. Here, mice deficient in apolipoprotein E (ApoE), a molecule associated with the etiology of Alzheimer's disease, served as a model to investigate the developmental and protective effects of SNV. In comparison to control animals, the deficient mice exhibited (a) reduced amounts of VIP messenger RNA; (b) decreased cholinergic activity (c) significant retardation in the acquisition of developmental milestones: forelimb placing behavior and cliff avoidance behavior; and (d) learning and memory impairments. Daily injections of SNV to ApoE-deficient newborn pups resulted in increased cholinergic activity and marked improvements in the time of acquisition of behavioral milestones, with peptide-treated animals developing as fast as control animals and exhibiting improved cognitive functions after cessation of peptide treatment. Specificity was demonstrated in that treatment with a related peptide (PACAP), pituitary adenylate cyclase-activating peptide, produced only limited amelioration. As certain genotypes of ApoE increase the probability of Alzheimer's disease, early counseling and preventive treatments may now offer an important route for therapeutics design.

Topics: Alzheimer Disease; Animals; Apolipoproteins E; Brain; Brain Diseases; Choline O-Acetyltransferase; Cholinergic Fibers; Learning; Memory Disorders; Mice; Mice, Knockout; Neuropeptides; Neuroprotective Agents; RNA, Messenger; Vasoactive Intestinal Peptide

Neurodegenerative diseases, in which neuronal cell disintegrate, bring about deteriorations in cognitive functions as is evidenced in millions of Alzheimer patients. A major neuropeptide, vasoactive intestinal peptide (VIP), has been shown to be neuroprotective and to play an important role in the acquisition of learning and memory. A potent lipophilic analogue to VIP now has been synthesized, [stearyl-norleucine17]VIP ([St-Nle17]VIP), that exhibited neuroprotection in model systems related to Alzheimer disease. The beta-amyloid peptide is a major component of the cerebral amyloid plaque in Alzheimer disease and has been shown to be neurotoxic. We have found a 70% loss in the number of neurons in rat cerebral cortical cultures treated with the beta-amyloid peptide (amino acids 25-35) in comparison to controls. This cell death was completely prevented by cotreatment with 0.1 pM [St-Nle17]VIP. Furthermore, characteristic deficiencies in Alzheimer disease result from death of cholinergic neurons. Rats treated with a cholinergic blocker (ethylcholine aziridium) have been used as a model for cholinergic deficits. St-Nle-VIP injected intracerebroventricularly or delivered intranasally prevented impairments in spatial learning and memory associated with cholinergic blockade. These studies suggest both an unusual therapeutic strategy for treatment of Alzheimer deficiencies and a means for noninvasive peptide administration to the brain.

Topics: Administration, Intranasal; Alzheimer Disease; Amyloid beta-Peptides; Animals; Aziridines; Cell Death; Cells, Cultured; Choline; Learning; Lipids; Male; Memory; Neuromuscular Blocking Agents; Neurons; Parasympatholytics; Rats; Rats, Wistar; Solubility; Structure-Activity Relationship; Vasoactive Intestinal Peptide

Neuropeptide concentrations were determined in the postmortem cerebral cortex from 19 cognitive-impaired schizophrenics, 4 normal elderly subjects, 4 multi-infarct dementia (MID) cases, and 13 Alzheimer's disease (AD) patients. Only AD patients met criteria for AD. The normal elderly and MID cases were combined into one control group. Somatostatin concentrations were reduced in both schizophrenia and AD. Neuropeptide Y concentrations were reduced only in schizophrenia, and corticotropin-releasing hormone concentrations were primarily reduced in AD. Concentrations of vasoactive intestinal polypeptide and cholecystokinin also were reduced in schizophrenia, although not as profoundly as somatostatin or neuropeptide Y. In AD, cholecystokinin and vasoactive intestinal peptide were unchanged. Neuropeptide deficits in schizophrenics were more pronounced in the temporal and frontal lobes than in the occipital lobe. The mechanisms underlying these deficits in schizophrenia and AD are likely distinct. In schizophrenia, a common neural element, perhaps the cerebral cortical gaba-aminobutyric acid (GABA)-containing neuron, may underlie these deficits.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Autopsy; Case-Control Studies; Cerebral Cortex; Cholecystokinin; Cognition; Corticotropin-Releasing Hormone; Dementia, Multi-Infarct; Female; Frontal Lobe; Humans; Male; Neuropeptides; Occipital Lobe; Schizophrenia; Schizophrenic Psychology; Somatostatin; Temporal Lobe; Vasoactive Intestinal Peptide

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Arginine Vasopressin; Brain Mapping; Circadian Rhythm; Female; Humans; Hypothalamic Diseases; Hypothalamus; Male; Middle Aged; Sleep Stages; Social Behavior Disorders; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide; Wakefulness

Recent studies have indicated that deposition of beta amyloid peptide in the brains of patients with senile dementia of the Alzheimer type (SDAT) is a consequence of abnormal processing of the beta amyloid protein precursor. In addition, reduced concentrations of various peptides have been measured in post-mortem brain tissue and cerebrospinal fluid (CSF) of patients with SDAT. We determined concentrations of the peptides derived from prepro-vasoactive intestinal peptide (VIP)--peptide histidine methionine-27 (PHM-27), peptide histidine valine (PHV) and VIP--and peptides derived from prepro-somatostatin (prepro-SS), SS-14 and SS-28, in CSF of patients with SDAT by radioimmunoassay combined with high performance liquid chromatography. We found significantly reduced levels of total PHM-immunoreactivity (IR) and PHV, and unaltered levels of PHM-27 and VIP in SDAT, compared with those in controls. Total SS-IR and SS-28 concentrations were significantly reduced in SDAT, while SS-14 levels did not differ from those of controls. These results suggest that an altered processing of the prepro-peptides of VIP and SS may occur in SDAT and that these alterations might have a significant role in the pathogenesis of SDAT.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Chromatography, High Pressure Liquid; Female; Humans; Male; Peptide Fragments; Protein Precursors; Radioimmunoassay; Somatostatin; Somatostatin-28; Vasoactive Intestinal Peptide

The concentrations of somatostatin (SRIF), vasoactive intestinal polypeptide (VIP), beta-endorphin (beta-EP), adrenocorticotropin (ACTH) and corticotropin-releasing factor (CRF) immunoreactivity were measured in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD), patients with Parkinson's disease (PD) and controls. In order to study the mechanisms that regulate peptide levels in CSF and peptide interactions, correlations between CSF peptides were determined. Within all patient groups a number of significant correlations were shown to exist between CSF peptides. The correlations were apparently not coincidental, since there was no such relation between the concentrations of CSF peptides and CSF protein content. Neither age, sex, severity of dementia nor the presence of extrapyramidal signs could explain the number of significant correlations. These results indicate, that the correlations found between CSF peptides may be due to common regulatory mechanisms or general physiological behaviour of peptides in the CSF.

Topics: Adrenocorticotropic Hormone; Aged; Aged, 80 and over; Alzheimer Disease; beta-Endorphin; Corticotropin-Releasing Hormone; Female; Humans; Male; Middle Aged; Neuropeptides; Parkinson Disease; Somatostatin; Vasoactive Intestinal Peptide

Cerebrospinal fluid (CSF) measures of dynorphin A were compared in three groups. Alzheimer patients (n = 9), elderly depressives (n = 9), and age-matched normal controls (n = 9). The Alzheimer patients revealed a 40% decrease in CSF dynorphin compared with controls (36 +/- 15 versus 60 +/- 21 pg/ml, p less than 0.05). In contrast, other peptide measures [Neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and galanin] remained unchanged across groups. This finding was further supported when an additional 20 Alzheimer patients with similar clinical backgrounds also showed reduced CSF dynorphin (37 +/- 13 pg/ml). CSF dynorphin did not correlate significantly with clinical variables or other CSF measures of monoamine metabolites [i.e., 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA)]. Given the previous report of increased kappa binding of Alzheimer brains at autopsy, the authors speculate about a possible up-regulation of opiate receptors in Alzheimer's disease and suggest ways to test this hypothesis in vivo.

Topics: Aged; Alzheimer Disease; Brain; Depressive Disorder; Dynorphins; Female; Galanin; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Male; Mental Recall; Methoxyhydroxyphenylglycol; Middle Aged; Neuropeptide Y; Neuropsychological Tests; Peptide Fragments; Peptides; Receptors, Opioid; Vasoactive Intestinal Peptide

Topics: Alzheimer Disease; Brain; Brain Chemistry; Cerebral Cortex; Cholecystokinin; Choline O-Acetyltransferase; gamma-Aminobutyric Acid; Hippocampus; Humans; Nerve Tissue Proteins; Neurofibrils; Neuropeptide Y; Neurotransmitter Agents; Norepinephrine; Psychological Tests; Vasoactive Intestinal Peptide

Neurofibrillary tangles are one of the histopathological neuronal abnormalities present in normal aging and especially in Alzheimer's Disease. We have utilized immunocytochemical staining for neuropeptides followed by Congo red with gallocyanin counterstaining and polarized illumination to determine whether enkephalin (Enk), somatostatin (Som), cholecystokinin (CCK), or vasoactive intestinal polypeptide (VIP) are contained in neurons afflicted with such tangles. A few Enk- or VIP-immunoreactive pyramidal cells in field hl and subiculum were found to contain tangles. Many such Enk- or VIP-immunoreactive neurons and cells containing Som- or CCK-like immunoreactivity did not contain such tangles.

Topics: Adult; Age Factors; Aged; Alzheimer Disease; Enkephalins; Female; Hippocampus; Humans; Immunoenzyme Techniques; Male; Middle Aged; Neurofibrils; Staining and Labeling; Time Factors; Vasoactive Intestinal Peptide

Somatostatin- and vasoactive intestinal polypeptide (VIP)-like immunoreactivities (SLI and VLI, respectively) were measured, by radioimmunoassay, in 21 regions of postmortem brains from 7 histologically verified cases of patients with Alzheimer-type dementia (ATD) and 10 histologically normal controls. SLI was significantly reduced in the orbital cortex, hippocampus and putamen of ATD brains. Significant reduction of VLI in the ATD brains was also found in the insular and angulate cortex, which have not previously been examined biochemically for peptides. These results suggest that involvement of not only somotostatin- but also VIP-containing neurons may not be ruled out in ATD brains.

Topics: Acetylcholine; Aged; Alzheimer Disease; Brain Chemistry; Cerebral Cortex; Choline O-Acetyltransferase; Dementia; Female; Humans; Male; Middle Aged; Somatostatin; Vasoactive Intestinal Peptide

Five neuropeptides (cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), somatostatin (SRIF), neurotensin (NT) and substance P (SP)) were measured in 14 brain areas (4 cortical areas, hippocampus, amygdala, 3 striatal areas, 2 thalamic areas and 3 subcortical areas-- septum, substantia innominata and hypothalamus) in 12 brains with neuropathologically confirmed Alzheimer type change and in 13 control brains. Choline acetyltransferase (CAT) activity was assessed in 6 of these areas. Levels of SRIF, but not those of the other peptides, were reduced in several cortical areas in Alzheimer-type dementia (ATD). The distribution and magnitude of the reduction in SRIF were less than that of CAT activity and the temporal cortex was the only region in which there was a significant relationship between CAT and SRIF deficits. Peptide levels were unchanged in hippocampus, amygdala, thalamus, hypothalamus and striatum (except for an increase in SP in the putamen). SRIF levels were increased in substantia innominata in ATD. NT and SRIF were significantly, and VIP and SP non-significantly, reduced in the septum in ATD. Thus, apart from these alterations in the septum, SRIF was the only neuropeptide for which major changes were identified and these did not follow either the pattern of neuropathological change (e.g. in amygdala and hippocampus) or of CAT deficits (e.g. in substantia innominata).

Topics: Aged; Alzheimer Disease; Brain; Brain Chemistry; Cholecystokinin; Choline O-Acetyltransferase; Female; Humans; Male; Nerve Tissue Proteins; Neurotensin; Reference Values; Somatostatin; Substance P; Tissue Distribution; Vasoactive Intestinal Peptide

Activities relating to 3 neurotransmitter and 4 neuropeptide systems have been examined in human temporal lobe (post mortem) for their relationships with age and Alzheimer-type changes (senile plaques and cognitive function). Significant alterations with increasing age (from 61 to 92 years) in a series of non-demented cases included a reduction of the cholinergic enzyme, choline acetyltransferase, and an increase in vasoactive intestinal peptide immunoreactivity. In cases of alzheimer's disease the only neurochemical activity investigated which correlated significantly with cognitive impairment (assessed from a Mental Test Score obtained shortly before death) and with the severity of Alzheimer-type abnormalities (senile plaques density) was choline acetyltransferase. Further analyses of the data in relation to the severity of plaque formation suggest that alterations in other neurochemical activities including reductions in dopamine-beta-hydroxylase activity, cholecystokinin octapeptide (aqueous extracted) and somatostatin immunoreactivities and an increase in substance P immunoreactivity, may occur at later stages of the disease process. These comparative data suggest that biochemical changes in this brain area associated with age and earlier stages of Alzheimer's disease may be relatively selective.

Topics: Aged; Aging; Alzheimer Disease; Cholecystokinin; Choline O-Acetyltransferase; Cognition; Dementia; Dopamine beta-Hydroxylase; Glutamate Decarboxylase; Humans; Middle Aged; Somatostatin; Substance P; Temporal Lobe; Vasoactive Intestinal Peptide

Vasoactive intestinal peptide (VIP) and cholecystokinin (CCK) have been measured, by radioimmunoassay, in cerebral cortex obtained at autopsy from patients without neurological or psychiatric disease and from patients with Alzheimer's disease, depression and schizophrenia. Sephadex gel filtration indicated that over 90% of the CCK immunoreactivity was associated with the octapeptide in extracted material from the different clinical groups investigated. There were no significant differences from the normal in the overall concentrations of either VIP or CCK in any of the psychiatric groups examined, although differences in Alzheimer's disease were apparent when cases were grouped according to postmortem delay.

Topics: Alzheimer Disease; Cerebral Cortex; Cholecystokinin; Dementia; Depressive Disorder; Gastrointestinal Hormones; Humans; Radioimmunoassay; Schizophrenia; Synaptic Transmission; Vasoactive Intestinal Peptide

Post-mortem brain tissue from 7 patients who died with a diagnosis of senile dementia of Alzheimer type (SDAT) was compared with tissue obtained from 7 control patients at routine post mortem. A significant fall in choline acetyltransferase (ChAT) activity was apparent in the cerebral cortex of the SDAT cases which was maximal in the temporal lobe. The fall in ChAT activity was not accompanied by changes in cortical vasoactive intestinal polypeptide (VIP) measured by radioimmunoassay.

Topics: Aged; Alzheimer Disease; Caudate Nucleus; Cerebral Cortex; Choline O-Acetyltransferase; Dementia; Female; Gastrointestinal Hormones; Globus Pallidus; Hippocampus; Humans; Interneurons; Male; Vasoactive Intestinal Peptide