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Metabolomic and lipidomic signatures in autosomal dominant and late‐onset Alzheimer's disease brains
Author(s) -
Novotny Brenna C.,
Fernandez Maria Victoria,
Wang Ciyang,
Budde John P.,
Bergmann Kristy,
Eteleeb Abdallah M.,
Bradley Joseph,
Webster Carol,
Ebl Curtis,
Norton Joanne,
Gentsch Jen,
Dube Umber,
Wang Fengxian,
Morris John C.,
Bateman Randall J.,
Perrin Richard J.,
McDade Eric,
Xiong Chengjie,
Chhatwal Jasmeer,
Goate Alison,
Farlow Martin,
Schofield Peter,
Chui Helena,
Karch Celeste M.,
Cruchaga Carlos,
Benitez Bruno A.,
Harari Oscar
Publication year - 2023
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12800
Subject(s) - psen1 , trem2 , metabolome , metabolomics , disease , biology , genetics , neurodegeneration , metabolite , alzheimer's disease , bioinformatics , medicine , presenilin , endocrinology , receptor , myeloid cells
The identification of multiple genetic risk factors for Alzheimer's disease (AD) suggests that many pathways contribute to AD onset and progression. However, the metabolomic and lipidomic profiles in carriers of distinct genetic risk factors are not fully understood. The metabolome can provide a direct image of dysregulated pathways in the brain. Methods We interrogated metabolomic signatures in the AD brain, including carriers of pathogenic variants in APP , PSEN1 , and PSEN2 (autosomal dominant AD; ADAD), APOE ɛ4, and TREM2 risk variant carriers, and sporadic AD (sAD). Results We identified 133 unique and shared metabolites associated with ADAD, TREM2, and sAD. We identified a signature of 16 metabolites significantly altered between groups and associated with AD duration. Discussion AD genetic variants show distinct metabolic perturbations. Investigation of these metabolites may provide greater insight into the etiology of AD and its impact on clinical presentation. HIGHLIGHTSAPP / PSEN1 / PSEN2 and TREM2 variant carriers show distinct metabolic changes. A total of 133 metabolites were differentially abundant in AD genetic groups. β‐citrylglutamate is differentially abundant in autosomal dominant, TREM2 , and sporadic AD. A 16‐metabolite profile shows differences between Alzheimer's disease (AD) genetic groups. The identified metabolic profile is associated with duration of disease.