Comorbid neuropathological diagnoses in early versus late-onset Alzheimer's disease

Copathologies play an important role in the expression of the AD clinical phenotype and may influence treatment efficacy. Early-onset AD (EOAD), defined as manifesting before age 65, is viewed as a relatively pure form of AD with a more homogeneous neuropathological substrate. We sought to compare the frequency of common neuropathological diagnoses in a consecutive autopsy series of 96 patients with EOAD (median age of onset = 55 years, 44 females) and 48 with late-onset AD (LOAD) (median age of onset = 73 years, 14 females). The UCSF Neurodegenerative Disease Brain Bank database was reviewed to identify patients with a primary pathological diagnosis of AD. Prevalence and stage of Lewy body disease (LBD), limbic age-related TDP-43 encephalopathy (LATE), argyrophilic grain disease (AGD), hippocampal sclerosis (HS), cerebral amyloid angiopathy (CAA), and vascular brain injury (VBI) were compared between the two cohorts. We found at least one non-AD pathological diagnosis in 98% of patients with EOAD (versus 100% of LOAD), and the number of comorbid diagnoses per patient was lower in EOAD than in LOAD (median=2 versus 3, Mann-Whitney Z = 3.00, p = 0.002). LBD and CAA were common in both EOAD and LOAD (CAA: 86% versus 79%, Fisher exact p = 0.33; LBD: 49% versus 42%, p = 0.48, respectively), although amygdala-predominant LBD was more commonly found in EOAD than LOAD (22% versus 6%, p = 0.02). In contrast, LATE (35% versus 8%, p