biostudies-literatureSepulveda-Falla DJoseph F. Arboleda-VelasquezNIA NIH HHSNIANACCNINDS NIH HHSNational Institutes of HealthNIHNIH HHS104-113https://www.ebi.ac.uk/biostudies/studies/S-EPMC11747142biostudies-literatureUnknown84(2)Studying comorbidities in early onset Alzheimer disease (AD) may provide an advantageous perspective on their pathogenesis because aging factors may be largely inoperative for these subjects. We compared AD comorbidities between early-onset sporadic cases and American and Colombian cases with PSEN1 mutations. AD neuropathological changes (ADNC) were very severe in all groups but more severe in the PSEN1 groups. Lewy body disease and cerebral white matter rarefaction were the most common (up to 60%) of AD comorbidities, followed by arteriolosclerosis (up to 37%), and large-vessel atherosclerosis (up to 20%). Differences between the 3 groups included earlier age of onset in the American PSEN1 cases, shorter disease duration in sporadic cases, and more frequent large-vessel atherosclerosis anJournal of neuropathology and experimental neurologyComorbidities in early-onset sporadic versus presenilin-1 mutation-associated Alzheimer disease dementia: Evidence for dependency on Alzheimer disease neuropathological changes.PMC11747142P30 AG062677P30 AG066514P30 AG066515R01 AG075802P30 AG072980P30 AG066518P30 AG066519P30 AG062715P20 AG068053R01 AG062479-01P30 AG072975P30 AG066462P30 AG072931P20 AG068077P30 AG072976P30 AG072977P30 AG066444P30 AG072972P30 AG072973P30 AG066468R01 AG062479P30 AG072978R01 AG079280P30 AG072979P30 AG072958P30 AG072959RF1 NS110048P30 AG062421P30 AG079280P30 AG062422P30 AG066546P30 AG066506P30 AG066507R01 AG056058P30 AG062429P30 AG066508P01AG025294P30 AG066509P01 AG025204P30 AG066530P20 AG068082P30 AG066511P30 AG066512U24 AG072122P20 AG068024P30 AG072946P30 AG072947Acosta-Uribe JGhetti BSerrano GESepulveda-Falla DMejia-Cupajita BVillalba-Moreno NDKofler JKVillegas Lanau CAKosik KSGlatzel MWhite Iii CBeach TGLu PFrosch MPRestrepo FLfalseComorbidities in early-onset sporadic versus presenilin-1 mutation-associated Alzheimer disease dementia: Evidence for dependency on Alzheimer disease neuropathological changes.Studying comorbidities in early onset Alzheimer disease (AD) may provide an advantageous perspective on their pathogenesis because aging factors may be largely inoperative for these subjects. We compared AD comorbidities between early-onset sporadic cases and American and Colombian cases with PSEN1 mutations. AD neuropathological changes (ADNC) were very severe in all groups but more severe in the PSEN1 groups. Lewy body disease and cerebral white matter rarefaction were the most common (up to 60%) of AD comorbidities, followed by arteriolosclerosis (up to 37%), and large-vessel atherosclerosis (up to 20%). Differences between the 3 groups included earlier age of onset in the American PSEN1 cases, shorter disease duration in sporadic cases, and more frequent large-vessel atherosclerosis an2025-01-01T00:00:00Z2025 Feb2026-05-02T03:45:27.273Z2025-04-04T01:32:24.522ZS-EPMC117471423965683210.1093/jnen/nlae122