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F2‐01‐01: NEURODEVELOPMENTAL DIFFERENCES AND ENVIRONMENTAL INSULTS INVERSELY CORRELATE WITH AGE OF ONSET IN ALZHEIMER'S DISEASE
Author(s) -
Miller Zachary A.,
Ossenkoppele Rik,
Shwe Wendy,
Allen Isabel Elaine,
Rosenberg Lynne M.,
Olguin Dustin,
Edwards Ken,
Ketelle Robin,
Karydas Anna M.,
Perry David C.,
Sturm Virginia,
Yokoyama Jennifer S.,
Desikan Rahul S.,
Geschwind Daniel H.,
Wolters Emma E.,
Flier Wiesje M.,
Pijnenburg Yolande A.L.,
Scheltens Philip,
Rademakers Rosa,
Graff-Radford Neill R.,
Rosen Howard J.,
Grinberg Lea T.,
Seeley William W.,
Miller Bruce L.,
Rabinovici Gil D.,
Gorno Tempini Maria Luisa
Publication year - 2019
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 - 10.1016/j.jalz.2019.06.4416
Subject(s) - dementia , medicine , disease , apolipoprotein e , early onset alzheimer's disease , cohort , diabetes mellitus , pediatrics , audiology , endocrinology
Disease Center AD, MCI and control participants was conducted for comparison. EV proteins were quantified by electrochemiluminescence assays. MRS glucose was measured through J-resolved MRS in a separate BLSA sub-cohort. Results: Mean EV diameter and levels of P-181-tau, P-231-tau, and phospho-inslulin receptor substrate 1 (IRS1) were higher in preclinical samples of BLSA participants that eventually developed AD compared to controls, with Receiver Operator Characteristic Area Under Curve of 90%, mid-80% sensitivity and specificity, and a 25.3 odds ratio. Results from a training set (2/3 of BLSA) were successfully replicated in a validation set (1/3 of BLSA). Longitudinal trajectories for various EV biomarkers depended heavily on age. Similar results were obtained for the cross-sectional cohort from Hopkins. On the other hand, AD patients showed step-wise higher MRS glucose than age-matched and young controls. Conclusions: EV biomarkers and MRS glucose can assist preclinical and clinical AD diagnosis and identify patients with abnormal underlying pathophysiologic processes. FEATURED RESEARCH SESSIONS F2-01 ATYPICAL ALZHEIMER’S DISEASE: GREAT EXPECTATIONS FROM THE UNEXPECTED