Individual environmental exposures, the exposome, can play an influential role in the development and progression of neurodegenerative diseases such as AD. We hypothesize that potentially modifiable risk factors of AD such as diabetes, hypertension, smoking, and alcohol consumption, in addition to the underexplored area deprivation index (ADI), could play a considerable role in severity of neuropathology and biochemical phenotypes of AD.

We evaluated 478 neuropathologically characterized AD donors, from the Mayo Clinic Brain Bank. 469 samples had available biochemical measures (APOE, Aβ40, Aβ42, tau, and phosphor-tau (Thr231)), collected across three isolated fractions (soluble (TBS), membrane-bound (TX), and insoluble (FA)) of the superior temporal gyrus. Exposome variables were extracted from the available records. Associations of ADI, diabetes, hypertension, smoking and alcohol with biochemical and neuropathology phenotypes were examined using linear regression, binary logistic regression and ordinal logistic regression models as appropriate given the nature of the outcome variable; all models were adjusted for age at death and sex.

Different components of the exposome impact levels of core AD proteins. Additional analyses in expanded cohorts to further explore the associations with neuropathology are ongoing. We expect that understanding how exposome impacts specific aspects of neurodegenerative diseases will provide key insights into underlying, potentially modifiable, mechanisms of disease.