neuropeptide-y and Dementia

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are two prevalent neurodegenerative disorders for which the causes are unknown, except in rare familial cases. Several changes in neuropeptide levels as measured by radioimmunoassay (RIA) have been observed in these illnesses. Somatostatin (SOM) levels in cerebrospinal fluid (CSF) are consistently decreased in AD and FTD. Neuropeptide Y (NPY) levels are decreased in AD, but normal in FTD. Galanin (GAL) levels increase with the duration of illness in AD patients. The majority of studies of neuropeptides in CSF have not been verified by HPLC. The observed decrease in a neuropeptide level as measured by RIA may therefore reflect an altered synthesis or extracellular processing, resulting in neuropeptide fragments that may or may not be detected by RIA. Matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-MS) has been shown to be a powerful technique in the analysis of biological materials without any pre-treatment, by detecting peptides and proteins at a specific mass-to-charge (m/z) ratio. We studied the processing of the neuropeptides NPY, NPY, SOM and GAL in the cerebrospinal fluid of patients with AD (n = 3), FTD (n = 3) and controls (n = 2) using MALDI-MS. We found that considerable inter-individual variability exists in the rate of neuropeptide metabolism in CSF, as well as the number of peptide fragments formed. Certain patients showed differences in the processing of specific neuropeptides, relative to other patients and controls. This analysis of the metabolic processing of neuropeptides in CSF yielded a large amount of data for each individual studied. Further studies are required to determine the changes in neuropeptide processing that can be associated with AD and FTD. With further investigations using MALDI-MS analysis, it may be possible to identify a neuropeptide fragment or processing enzyme that can be correlated to these disease states.

Topics: Alzheimer Disease; Case-Control Studies; Dementia; Female; Galanin; Humans; Male; Middle Aged; Neuropeptide Y; Somatostatin; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Much is known about modular organization in the cerebral cortex, but this knowledge is skewed markedly toward primary sensory areas, and in fact, it has been difficult to demonstrate elsewhere. In this report, we test the hypothesis that a unique form of modules exists in the entorhinal area of the human cortex (Brodmann's area 28). We examined this issue using classic cyto- and myeloarchitectonic stains, immunolabeling for various neurochemicals, and histochemistry for certain enzymes. The findings reveal that the entorhinal cortex in the human is formed by a mosaic of cellular aggregates whose most conspicuous elements are the cell islands of layer II and myelinated fibers around the cell islands, the disposition of glutamic acid decarboxylase-positive neurons and processes, cytochrome oxidase staining, and the pattern of cholinergic afferent fibers. The neuropathology of Alzheimer's disease cases highlights the modules, but inversely so, by destroying their features. The findings are of interest because 1) anatomically defined modules are shown to be present in areas other than the sensory and motor cortices, 2) the modules are morphological entities likely to reflect functions of the entorhinal cortex, and 3) the destruction of entorhinal cortex modules may account disproportionately for the severity of memory impairments in Alzheimer's disease.

Topics: Acetylcholinesterase; Adolescent; Adult; Aged; Aged, 80 and over; Alzheimer Disease; Child; Child, Preschool; Dementia; Electron Transport Complex IV; Glutamate Decarboxylase; Glutaminase; Hippocampus; Histocytochemistry; Humans; Immunohistochemistry; Middle Aged; Neurons; Neuropeptide Y; Parvalbumins; Reference Values; Somatostatin

Neuropeptide Y (NPY) has been shown to be involved in the control of several neuroendocrine functions. Moreover, in animal models, NPY produces behavioral effects that are similar to those induced by anxiolytics. We studied NPY-like immunoreactivity (NPY-LI) in cerebrospinal fluid (CSF) in two primary degenerative dementias, Alzheimer disease (AD, n = 34) and frontotemporal dementia (FTD, n = 22) and correlated the CSF NPY-LI levels with clinical characteristics, as rated with the Organic Brain Syndrome scale. There were significant correlations between NPY-LI and such clinical items as suspiciousness, anxiousness, restlessness-agitation, and irritability in both AD and FTD. AD patients, but not FTD patients, showed a significant negative correlation between NPY-LI and duration of the disease. Thus, the study found significant correlations between CSF NPY-LI and emotional symptoms and behavior in organic dementia.

Topics: Adult; Aged; Aggression; Alzheimer Disease; Anxiety; Dementia; Female; Humans; Male; Middle Aged; Neuropeptide Y; Paranoid Disorders; Radioimmunoassay

The CSF levels of somatostatin-LI (SLI), neuropeptide Y (NPY-LI) and Delta Sleep Inducing Peptide (DSIP-LI) have been measured in patients with dementia of Alzheimer type (DAT) and dementia with frontotemporal degeneration of non-Alzheimer type (FTD). The distribution pattern of cortical degeneration differs between these two types of dementia. DAT shows degeneration of mainly temporo-parietal and temporo-limbic structures, whereas FTD discloses its main degeneration in the frontotemporal regions (Brun, 1987). The somatostatin-LI was significantly reduced both in DAT and FTD. NPY-LI showed a significant reduction in DAT but not in FTD. A tendency to a reduction with duration of the disease was observed in DAT whereas the contrary was noted in FTD. The DSIP-LI levels were reduced in DAT and slightly increased in FTD. The study provides an evidence of neurochemical differences between the two primary degenerative dementias.

Topics: Adult; Aged; Alzheimer Disease; Delta Sleep-Inducing Peptide; Dementia; Female; Frontal Lobe; Humans; Male; Middle Aged; Neuropeptide Y; Neuropeptides; Somatostatin; Temporal Lobe

Cerebrospinal fluid somatostatin and neuropeptide Y concentrations were measured in 26 healthy normal subjects, 27 patients with dementia of the Alzheimer type (DAT), and seven patients with DAT with extrapyramidal signs (EDAT). In healthy normal subjects, there was no significant correlation between age and either somatostatin or neuropeptide Y concentration. However, the concentrations of both peptides correlated significantly with each other. In patients with DAT and EDAT, the concentrations of somatostatin (17.5 +/- 5.0 and 16.4 +/- 5.0 pg/mL, respectively) were significantly reduced relative to age-matched control subjects (23.1 +/- 8.2 pg/mL) but were unrelated to dementia severity and did not change significantly during the progression of the disease. Neuropeptide Y concentrations did not differ significantly between the age-matched control, DAT, and EDAT groups (38.2 +/- 12.8, 37.0 +/- 12.3, and 30.3 +/- 7.8 pg/mL, respectively). These results suggest that in DAT, dysfunction of cortical somatostatin but not neuropeptide Y transmitter systems is reflected by reduced cerebrospinal fluid concentrations.

Topics: Adult; Aged; Aged, 80 and over; Aging; Alzheimer Disease; Dementia; Extrapyramidal Tracts; Female; Humans; Male; Middle Aged; Neuropeptide Y; Somatostatin