Different Sides of Depression in the Elderly: An In-depth View on the Role of Aβ Peptides

Background: Late-onset depression (LOD) is the most common neuropsychiatric disorder associated with Alzheimer's disease (AD), often associated with structural and functional brain changes, neuropsychological impairments and negative family history for affective disorders. LOD could be a risk factor or a prodromal phase of AD; this has led to the investigation of the link between depression and amyloid-beta (A beta) peptides by measuring A beta levels in plasma, cerebrospinal fluid (CSF) and brains of elderly depressed subjects. Objective: This study aims to clarify the complex relationship between depression, A beta peptides and AD. Methods: We evaluated all articles published up to 2019 in PubMed in which A beta was measured in serum (or plasma), CSF or brain in elderly with Major Depressive Disorder or depressive symptoms evaluated with standard scales. Results: Low plasma A beta 42 levels are strongly associated with depression severity. Plasma A beta 40 levels are higher in younger depressed, drug-resistant and those with more severe symptoms. CSF A beta 42 levels are lower in depressed than controls. PET-detected global and region-specific increases in A beta deposition are sometimes associated with LOD, cognitive impairment, anxiety but not with Cardiovascular Diseases (CVDs)/CVD risk factors. Elderly depressed with CVDs/CVD risk factors have more frequently high plasma A beta 40 levels and drug-resistance; those without these co-morbidities have low plasma A beta 42 levels and greater cognitive impairment. Conclusion: Two specific A beta profiles emerge in the depressed elderly. One is associated with A beta 42 reductions in plasma and CSF, possibly reflecting increased brain amyloid deposition and prodromal AD. The other one is characterized by high plasma A beta 40 levels, cerebrovascular disease and is clinically associated with increased AD risk.

Automated summary

Late-onset depression (LOD) is closely related to Alzheimer's disease (AD) and has complex connections with amyloid-beta (Aβ) peptides. Low plasma Aβ42 levels are strongly associated with depression severity, while high plasma Aβ40 levels are associated with younger depressed individuals, drug-resistant depression, and more severe symptoms.