Abstract Body

Objectives: The nucleus basalis of Meynert (nbM), a major cholinergic hub, is selectively vulnerable to neurofibrillary tangle pathology in Alzheimer’s disease (AD, Hanna Al-Shaikh 2020). Our goal is to examine demographic modifiers of this vulnerability to examine the contribution of age, sex, and occupation.
Methods: The FLorida Autopsied Multi-Ethnic (FLAME) cohort was examined for neurofibrillary tangle accumulation utilizing thioflavin-S microscopy to identify mature and extracellular tangles in the anterior nbM. Age at onset of cognitive problems and highest level of occupation (scaled to 0-6) was retrospectively examined. AD cases lacking known mutations were examined and age 65 was used to stratify young onset AD (YOAD) and late onset AD (LOAD).
Results: YOAD cases had nearly twice the number of tangles (median=16) compared to LOAD (median=9, p<0.001). YOAD also had fewer neurons (median=21/mm²) than LOAD (median=27/mm², p<0.001). Regression analysis of greater tangle accumulation in the nbM revealed younger age (p<0.001), higher Braak stage (p<0.001), and presence of Lewy body disease (p<0.001) as significant predictors, but not sex, occupation, or presence of APOE-ε4. Regression analysis of higher neuronal density in the nbM revealed older age (p<0.001), lower Braak stage (p<0.001), lack of Lewy body disease (p<0.001), and higher occupation level (p=0.020) as significant predictors, but not sex or presence of APOE-ε4.
Conclusions: In addition to age, severity of disease course and co-occurrence of Lewy body disease should be considered when investigating selective vulnerability of the nbM. Interestingly, occupation may modify neuronal volume of the nbM, but not necessarily spare accumulation of pathology.