Presence of co‐pathology in sporadic early‐onset Alzheimer disease versus dominantly inherited Alzheimer disease. (December 2021)

• Record Type: Journal Article
• Authors: Llibre‐Guerra, Jorge J; Li, Yan; Franklin, Erin E.; Miller, Carol A; Teich, Andrew F; Kofler, Julia; Dickson, Dennis W; Ghetti, Bernardino Francesco; Frosch, Matthew P.; Halliday, Glenda M; McLean, Catriona; Lashley, Tammaryn; Gordon, Brian A.; Schindler, Suzanne E.; Chen, Charles D.; Fagan, Anne M.; Benzinger, Tammie L.S.; Wang, Guoqiao; Hassenstab, Jason; Morris, John C.; Bateman, Randall J.; Perrin, Richard J.; McDade, Eric
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 3
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.055045
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: A small proportion of Alzheimer disease (AD), known as early onset AD (EOAD), has symptomatic age at onset (AAO) before age 65. About 5‐10% of EOAD is dominantly inherited (DIAD); the rest is termed to be sporadic (sEOAD). Although DIAD and sEOAD share the hallmark plaques and tangles that define AD neuropathologic change (ADNC), the relative burdens of these lesions and the frequencies of non‐AD co‐pathologies in sEOAD relative to DIAD remain unknown. Methods: We compared the neuropathological burden of AD and the frequency of AD and non‐AD pathologies in 363 sEOAD cases from the National Alzheimer's Coordinating Center (NACC) and in 62 DIAD cases (45 from the Dominantly Inherited Alzheimer Network (DIAN); 17 from NACC). Operational criteria for the classification of AD and other co‐pathologies followed accepted NACC guidelines. Only cases with AAO under 65 and a primary pathological diagnosis of 'high ADNC' were included. Results: DIAD participants [mean AAO = 42.9 ± 8.1 years] had higher CERAD scores than sEOAD cases [mean AAO = 57.1 ±7.2 years] [p=0.03]. Braak stages were similar for both cohorts. The frequency and severity of cerebral amyloid angiopathy (CAA) was higher in DIAD versus sEOAD [CAA: 100% vs 83.7%, p=0.001; severe CAA: 40.3% versus 20.1%, p<0.001, respectively]. The frequency of at least one non‐AD/non‐CAA pathology was similar between DIAD and sEOAD [63.9% vs 59.7%, p=0.61], but the frequency of multiple pathologies (two or more) was lower in DIAD [3.2%] than in sEOAD [21.0%, p<0.001]. Lewy body disease (LBD) was the most prevalent non‐AD/non‐CAA pathology in both cohorts [58.1% in DIAD, 51.2% in sEOAD; p=0.39]. Hippocampal sclerosis [14.5%] and argyrophilic grain disease [2.5%], were observed in sEOAD, but were absent from DIAD. Conclusions: DIAD cases show greater neuritic plaque density and more severe CAA than sEOAD cases, but comparable Braak NFT stages. The similar frequencies of LBD in both cohorts may be linked to severe AD neuropathological change, rather than co‐incident age‐related pathologies. Future studies should include methodologically uniform assessments of both cohorts to explore age‐related and non‐age‐related mechanisms that may account for differences in the burdens of ADNC lesions and non‐AD co‐pathologies.