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O4–02–03: Using cerebrospinal fluid markers to identify stages of National Institute on Aging and Alzheimer's Association proposed criteria for preclinical Alzheimer's disease and its prognosis
Author(s) -
Vos Stephanie,
Xiong Chengjie,
Grant Elizabeth,
Visser Pieter Jelle,
Cairns Nigel,
Morris John,
Holtzman David,
Fagan Anne
Publication year - 2013
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.2013.04.342
Subject(s) - clinical dementia rating , dementia , medicine , stage (stratigraphy) , disease , alzheimer's disease , cognitive decline , apolipoprotein e , pittsburgh compound b , oncology , pathology , biology , paleontology
positron emission tomography (PiB-PET) data, were grouped based upon cognitive change and changes in measurable levels of PiB-PET over 36 months. Participants were classified as those who transitioned for cognitive decline and PiB-PET levels, those healthy controls that did not transition and stable AD participants over 36 months. Four isoforms of plasma betaamyloid were measured: Ab1 40, Ab1 42, n-terminally truncated Abn 40, and Abn 42, and the relative ratios calculated at baseline and at 18 months. Results: Compared with the non-transition group, the transition group demonstrated a significantly greater change in PiB-PET scores between baseline and 36 month time points (P1⁄48.81 *-05). Change in both composite memory and non-memory scores were significantly greater in participants from the transition group when compared to the non-transition group (composite memory score, P1⁄40.002, composite non-memory score P<0.0001). Comparisons of plasma beta-amyloid levels between the transition and non-transitional groups showed Ab1 42 and the Ab1 42/Ab1 40 ratio were significantly different at baseline (P1⁄40.008 and P1⁄40.002, respectively) and at 18 months (P1⁄40.003 and P1⁄40.004, respectively). Conclusions: Using one of the world’s largest longitudinal studies of aging with serial PiB-PET measurements, we created clinically functional cognitive change groups that matched changes in PiB-PET. We demonstrated that baseline plasma Ab1 42 and the Ab1 42/Ab1 40 ratio were putative biomarkers indicative of cognitive decline, which were validated using 18 month data. These findings suggest that longitudinal plasma beta-amyloid can contribute to a pre-symptomatic biomarker panel for AD.