amyloid-beta-peptides and Depressive-Disorder--Major

Epidemiological studies have demonstrated that depression may be a risk factor for Alzheimer's disease (AD); however, the biological mechanisms of the transition from depression to AD are still not clear. Changes of amyloid β protein (Aβ) metabolism and increased glucocorticoid (GC) levels have been found in both depression and AD. Moreover, several studies in animal models have demonstrated that GC administration changes Aβ metabolism. To reveal whether GC affects amyloid metabolism in patients with depression, we evaluated serum levels of Aβ40, Aβ42 and cortisol at admission in 187 inpatients with major depressive disorder (MDD) and 224 healthy comparisons. Additionally, we re-evaluated the serum levels of Aβs in 27 patients with MDD 1 year later. The results of multiple regression analyses revealed that serum cortisol and Aβ levels are not correlated at the time of admission. However, serum cortisol levels at admission correlated with serum Aβ42 levels and Aβ40/Aβ42 ratio 1 year later. These findings suggest that increased cortisol in patients with MDD may influence the metabolism of Aβ over prolonged periods of time.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Animals; Depressive Disorder, Major; Female; Glucocorticoids; Humans; Hydrocortisone; Male; Middle Aged; Peptide Fragments; Regression Analysis; Time Factors

Depression has been linked to Alzheimer's disease as either an increased risk factor for its development or as a prodromal symptom. The neurobiological basis for such an association, however, remains poorly understood. Numerous studies have examined whether changes in amyloid beta (Aβ) metabolism, which are implicated in the pathogenesis of Alzheimer's disease, are also found in depression. In this paper, we investigated the relationship between depressive symptoms and cerebrospinal fluid (CSF) Aβ indices in otherwise healthy, cognitively normal elderly with late-life major depression (LLMD) and controls using a longitudinal approach, which is a novel contribution toward the literature. Significantly lower levels of CSF Aβ42 were observed in the LLMD group at baseline and were associated with more severe depressive symptoms. During longitudinal follow-up, the depressed group remained cognitively unchanged, but was significantly less depressed than at baseline. A greater improvement in depressive symptoms was associated with increases in CSF Aβ42 levels in both groups. Increases in CSF Aβ42 and Aβ40 were also associated with increased CSF total-tau levels. Our results suggest that LLMD may be associated with state-dependent effects of CSF Aβ42 levels. Future studies should determine whether the association reflects state-dependent changes in neuronal activity and/or brain amyloid burden in depression.

Topics: Aged; Aged, 80 and over; Aging; Amyloid beta-Peptides; Case-Control Studies; Depressive Disorder, Major; Female; Humans; Longitudinal Studies; Male; Middle Aged; Peptide Fragments; Psychiatric Status Rating Scales; tau Proteins

It has been suggested that sleep-wake regulation as well as hypocretins play a role in the pathophysiology of Alzheimer's disease. We analyzed Aβ40, Aβ42, Tau protein, phosphorylated Tau (pTau) protein as well as hypocretin-1 concentrations in the CSF of a detection sample of 10 patients with Alzheimer's disease (AD) as well as 10 age- and gender-matched patients with major depression as a comparison group of different pathology. In order to replicate the findings, we used a confirmation sample of 17 AD patients and 8 patients with major depression. We found hypocretin-1 concentrations in CSF not to differ between patients with depression and AD. However, hypocretin-1 was significantly related to Tau (r=0.463, p<0.001) and pTau (r=0.630, p<0.0001). These effects were more pronounced in depressed patients when compared to AD patients. We conclude that hypocretin-1 may play a role in the metabolism of Tau proteins across different diagnostic entities including AD. It has to be determined whether there is a causal relationship between hypocretin-1 and Tau as well as pTau.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Depressive Disorder, Major; Female; Humans; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; Neuropeptides; Orexins; Peptide Fragments; Phosphorylation; tau Proteins

Epidemiological studies have proposed that depression may increase the risk for Alzheimer's disease (AD), even in patients with early-onset depression. Although metabolism of amyloid β protein (Aβ) in elderly depression received attention in terms of their correlation, there is a serious heterogeneity in elderly depression in terms of age at onset of depression. Moreover, it is unknown whether early-onset major depressive disorder (MDD) has a long-term effect on the involvement of Aβ metabolism and later development of AD. Thus, we evaluated serum Aβ40 and Aβ42 levels, the Aβ40/Aβ42 ratio in 89 elderly (≥60 years of age) inpatients with MDD and 81 age-matched healthy controls, and compared them among patients with early-onset (<60 years) and late-onset (≥60years) MDD and controls. The results showed that the serum Aβ40/Aβ42 ratio was significantly higher in patients with both early- and late-onset MDD than in controls (early-onset, p=0.010; late-onset, p=0.043), and it is of great interest that the serum Aβ40/Aβ42 ratio was negatively correlated with the age at MDD onset (R=-0.201, p=0.032). These results suggest that an earlier onset of MDD may have a more serious abnormality in Aβ metabolism, possibly explaining a biological mechanism underlying the link between depression and AD.

Topics: Age of Onset; Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Antidepressive Agents; Apolipoprotein E4; Cerebrovascular Disorders; Data Interpretation, Statistical; Depression; Depressive Disorder, Major; Female; Humans; Intelligence; Male; Middle Aged; Neuropsychological Tests; Peptide Fragments; Risk; Socioeconomic Factors

Epidemiologic studies have demonstrated that a history of depression increases the risk of developing Alzheimer's disease, particularly among individuals with early-onset depression. On the other hand, recent studies have suggested that a higher amyloid-β protein (Aβ)40 to Aβ42 ratio may be associated with the future onset of Alzheimer's disease. Our objective was to assess whether the pathophysiology of early-onset depression may involve or affect Aβ metabolism.. In this extension of a case-control pilot study, 193 inpatients with DSM-IV major depressive disorder (MDD) (mean age = 55.9 years) from the Juntendo Koshigaya Hospital, Saitama, Japan, and 413 healthy controls from the community (mean age = 56.6 years) were recruited between May 2004 and April 2009. Serum Aβ40 and Aβ42 levels, Aβ40/Aβ42 ratio, and other clinical and biological factors were compared between controls and patients in 3 age groups: young (< 40 years), middle-aged (≥ 40 to < 65 years), and elderly (≥ 65 years). Depressive symptoms were assessed with the Hamilton Depression Rating Scale. All patients were receiving antidepressant medication at the time of the study, and doses of current antidepressants were converted to an equivalent imipramine dose.. The serum Aβ40/Aβ42 ratio was significantly higher in MDD patients than controls in all age groups (young: P = .003; middle-aged: P < .001; elderly: P = .006). These differences were also observed in noncarriers of the apolipoprotein E ε4 allele.. Our findings suggest that Aβ metabolism may be affected in depression; these findings also possibly answer the question of why even early-onset depression is a risk factor for developing Alzheimer's disease.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Alleles; Amyloid beta-Peptides; Apolipoprotein E4; Biomarkers; Case-Control Studies; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Peptide Fragments; Pilot Projects

Topics: Aging; Amyloid beta-Peptides; Dementia; Depressive Disorder, Major; Female; Humans; Male; Mental Disorders; Peptide Fragments

Depression may increase the risk of developing Alzheimer's disease (AD). Recent large cohort studies have also shown that a low plasma amyloid beta (Abeta)-42 level combined with a high Abeta40 level increases the risk of developing AD, suggesting plasma Abeta42/40 ratio as useful for identifying risk of developing mild cognitive impairment and AD. Although several studies have examined Abeta levels in the peripheral blood of elderly individuals with depression, results have been inconsistent. Furthermore, no results have been described for younger depression.. Serum Abeta40, Abeta42 level and Abeta40/42 ratio were evaluated using enzyme-linked immunosorbent assay in 60 patients with major depressive disorder (MDD) and 60 healthy controls. The results were analyzed in two age groups (young, <60 years; elderly, >or=60 years).. Serum Abeta40 level was significantly higher in young MDD patients compared to young controls (P < 0.001), but it was not significantly deferent in the elderly group. Serum Abeta42 level did not differ significantly in both young and elderly groups. Abeta40/42 ratio was significantly higher in both young (P < 0.001) and elderly (P < 0.001) patients with MDD compared to controls.. Serum Abeta40/42 ratio was significantly higher in MDD patients than in controls, and this difference was seen for both elderly and young subjects. This may suggest that even young subjects with MDD undergo pathological changes in the very early stage of amyloid deposition.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Amyloid beta-Peptides; Depressive Disorder, Major; Enzyme-Linked Immunosorbent Assay; Female; Humans; Japan; Male; Middle Aged; Peptide Fragments; Pilot Projects; Reference Values