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

Abstract

To explore markers for synaptic function and Alzheimer disease (AD) pathology in late life depression (LLD), predementia AD and normal controls (NC). A cross-sectional study to compare cerebrospinal fluid (CSF) levels of neurogranin (Ng), Beta-site amyloid-precursor-protein cleaving enzyme1 (BACE1), Ng/BACE1 ratio and Amyloid-β 42/40 ratio, phosphorylated-tau and total-tau in LLD with (LLD AD) or without (LLD NoAD) AD pathology, predementia AD and normal controls (NC). We included 145 participants (NC = 41; predementia AD = 66 and LLD = 38). LLD comprised LLD AD (n = 16), LLD NoAD (n = 19), LLD with non-AD typical changes (n = 3, excluded). LLD AD (pADJ < 0.05) and predementia AD (pADJ < 0.0001) showed significantly higher Ng than NC. BACE1 and Ng/BACE1 ratio were altered similarly. Compared to LLD NoAD, LLD AD showed significantly higher Ng (pADJ < 0.001), BACE1 (pADJ < 0.05) and Ng/BACE1 ratio (pADJ < 0.01). All groups had significantly lower Aβ 42/40 ratio than NC (predementia AD and LLD AD, p < 0.0001; LLD NoAD, p < 0.05). Both LLD groups performed similarly on tests of memory and executive function, but significantly poorer than NC. Synaptic function in LLD depended on AD pathology. LLD showed an association to Amyloid dysmetabolism. The LLD groups performed poorer cognitively than NC. LLD AD may be conceptualized as “predementia AD with depression”.

Comparative analysis of multimodal biomarkers for amyloid-beta positivity detection in Alzheimer's disease cohorts

“…The multi-site DDI cohort study comprised at-risk and clinical cases with subjective cognitive decline (SCD) (Jessen et al, 2014 ) and MCI (Albert et al, 2011 ) who had standardized MRI and CSF measurements (Fladby et al, 2017 ; Siafarikas et al, 2021 ). In addition, healthy controls (HC) were included from spouses of patients and from patients who completed lumbar punctures in connection with orthopedic surgery.…”

“…More specifically, we categorized patients with 18F-AV-45 values ≥1.11 into the Aβ+ group, while those with values below this threshold were assigned to the Aβ− group. In the DDI dataset, we established Aβ42/40 ratio cutoffs with a range of 0.077, derived from receiver operating curve (ROC) analysis using visual read results of Flutemetamol (18F-Flut) PET scans as the standard reference (Siafarikas et al, 2021 ). Aβ measurements were excluded from predictor variables in the model, as they were partially used for status definition in DDI and represent the same features as measured with PET in ADNI.…”

Stable cerebrospinal fluid neurogranin and β-site amyloid precursor protein cleaving enzyme 1 levels differentiate predementia Alzheimer’s disease patients

“…An optimum cut-off for Aβ 42/40 ratio at ≤0.077 was determined following receiver operating curve (ROC) analysis using visual read of [18F]-Flutemetamol PET scans as the standard of truth. 50 We selected three groups based on the A/T/N staging at baseline: (i) cases with amyloid pathology without tau pathology (A+/T−/N−, n = 86), (ii) cases with both amyloid pathology and tau pathology (A+/T+/N+, n = 90), and (iii) healthy controls with normal CSF Alzheimer’s disease biomarkers (A−/T−/N−, n = 74). Longitudinally collected CSF samples were available for subsets from all groups (A-/T-/N-: n = 33; A+/T-/N-: n = 39; A+/T+/N+: n = 28) at approximately 2-year intervals ranging between one and 6 years from baseline (see Supplementary Table 1 for details).…”

Roles of traditional chinese medicine regulating neuroendocrinology on AD treatment

“…Studies have shown that cardiovascular diseases, metabolic disorders, endocrine disorders, anxiety and depression are all risk factors for the development of AD. Early intervention of related risk factors have been proved to have an effect on reducing the risk of AD, even reversing the cognitive loss of MCI patients and delaying the progress of the disease ( 6 , 7 ).…”