Cerebrospinal fluid markers for synaptic function and Alzheimer type changes in late life depression

Area of Science:

• Neuroscience
• Gerontology
• Psychiatry

Background:

• Late-life depression (LLD) is associated with increased risk of Alzheimer disease (AD).
• Identifying biomarkers for synaptic function and AD pathology in LLD is crucial for understanding disease mechanisms.
• Distinguishing LLD with and without AD pathology is important for potential therapeutic strategies.

Purpose of the Study:

• To investigate cerebrospinal fluid (CSF) markers of synaptic function and AD pathology in LLD, predementia AD, and normal controls (NC).
• To explore the relationship between AD pathology and cognitive function in LLD.
• To determine if LLD with AD pathology can be conceptualized as a predementia AD state.

Main Methods:

• Cross-sectional study comparing CSF levels of neurogranin (Ng), BACE1, Aβ 42/40 ratio, p-tau, and t-tau.
• Included 145 participants: NC (n=41), predementia AD (n=66), LLD (n=38) including LLD with AD pathology (LLD AD, n=16) and LLD without AD pathology (LLD NoAD, n=19).
• Cognitive assessments for memory and executive function were performed.

Main Results:

• LLD AD and predementia AD showed significantly higher Ng levels than NC.
• BACE1 and Ng/BACE1 ratio were altered similarly in LLD AD and predementia AD.
• All LLD and predementia AD groups had significantly lower Aβ 42/40 ratio than NC.
• LLD groups performed poorer on cognitive tests than NC, with no significant difference between LLD AD and LLD NoAD.
• Synaptic function in LLD was dependent on the presence of AD pathology.

Conclusions:

• LLD is associated with amyloid dysmetabolism.
• LLD AD may be conceptualized as a predementia AD state characterized by depression.
• Synaptic function in LLD is influenced by underlying AD pathology, highlighting the interplay between depression and AD.