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P1–187: Lack of agreement between biomarkers of neuronal injury in ADNI
Author(s) -
Kriett Laura,
Förster Stefan,
Drzezga Alexander,
Fellgiebel Andreas,
Yakushev Igor
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.2013.05.410
Subject(s) - neuroimaging , alzheimer's disease neuroimaging initiative , medicine , neuropsychology , atrophy , psychology , cognitive impairment , cohort , pathophysiology , pathology , oncology , disease , cognition , neuroscience
Background: Alzheimer’s disease (AD) is marked by cerebrovascular dysfunction and dysregulation of b-amyloid (Ab) processes, both of which increase with age. Little is known, however, about the relationship between cerebral blood flow, CSF measures and age in cognitively normal adults in the preclinical stages of AD. Identifying brain biomarkers of AD risk in this group could help promote preclinical diagnosis of AD and early intervention and prevention strategies. OBJECTIVE: To characterize the relationship between relative cerebral blood flow (rCBF), CSF biomarkers, and age in asymptomatic middle-aged adults with a parental history of AD. Methods: CSF biomarkers were measured in 96 non-demented, middleaged adult children of persons with AD (mean6SD; age1⁄453.568.0yrs; n1⁄466 [69%] women; n1⁄435 [36%] apolipoprotein E ε4 allele carriers [APOE4+]). Among this group, 42 participants (age1⁄453.866.9yrs; n1⁄430 [71%] women; n1⁄414 [33%] APOE4+) underwent 1.5T-DSC perfusionweighted MRI scans which were used to estimate measures of rCBF. CSF b-amyloid1-42 (Ab1-42), total-tau (T-tau) and phosphorylated tau (P-tau 181) were analyzed using the INNO-BIA AlzBio3 (xMAP) assay. CSF Abx-38, Abx-40 and Abx-42 were measured using Meso Scale Discovery (MSD ) electrochemiluminescence. Results: A semi-partial regression model controlling for systolic blood pressure (SBP) and APOE4 status revealed that age was a) negatively associated with rCBF within a region of left parahippocampal gyrus (PHG) (Figure) and b) positively associated with seven CSF measures: Abx-38, Abx-40, Abx-42, T-tau, P-tau 181, the ratio (T-tau)/(Ab42), and the ratio (P-tau 181)/(Ab42). CBF within left PHG, however, was not associated with any of the CSF measures when controlling for age. Conclusions: In asymptomatic adult children of persons with AD, CBF and CSF biomarkers are significantly associated with increasing age but appear to be independent of each other in the preclinical stages of the disease. Whereas cerebrovascular dysfunction and Ab dysregulation likely interact and accelerate neurodegeneration later in the disease course, these processes may not interact with each other as strongly during this asymptomatic stage. The temporal point at which CBF and Ab processes significantly affect each other requires further longitudinal investigation.