• Liang Wang, Tammie L Benzinger, Jason Hassenstab, Tyler Blazey, Christopher Owen, Jingxia Liu, Anne M Fagan, John C Morris, and Beau M Ances.
• From the Departments of Neurology (L.W., J.H., T.B., A.M.F., J.C.M., B.M.A.), Radiology (T.L.B., C.O., B.M.A.), Psychology (J.H.), and Neurosurgery (T.L.B.), The Charles F. and Joanne Knight Alzheimer's Disease Research Center (T.L.B., J.H., A.M.F., J.C.M., B.M.A.), The Hope Center for Neurological Disorders (A.M.F., J.C.M., B.M.A.), and Division of Biostatistics (J.L.), Washington University in Saint Louis, MO.
• Neurology. 2015 Mar 24; 84 (12): 1254-60.

ObjectivesTo determine whether an MRI-based Alzheimer disease (AD) signature biomarker can detect tau-related neurodegeneration in preclinical AD, and to assess whether AD signature cortical thinning is associated with cognitive changes in cognitively normal (CN) older individuals.MethodsIn a large cohort of CN individuals (n = 188), we measured the hippocampal volume and cortical thickness within independently defined AD signature regions. We cross-sectionally assessed the associations between AD signature cortical thinning or hippocampal atrophy with CSF biomarkers of tau (increased tau) and β-amyloid (Aβ) (decreased Aβ42). We also examined the impact of AD signature cortical thinning or other biomarker changes (i.e., hippocampal atrophy, reduced CSF Aβ42, or increased CSF tau) on cognitive performance in CN individuals.ResultsElevated CSF tau was associated with AD signature cortical thinning but not hippocampal atrophy. In contrast, decreased CSF Aβ42 was associated with hippocampal loss but not AD signature cortical thinning. In addition, AD signature cortical thinning was associated with lower visuospatial performance. Reduced CSF Aβ42 was related to poorer performance on episodic memory.ConclusionsSpatially distinct neurodegeneration is associated with Aβ and tau pathology in preclinical AD. Aβ deposition and AD signature cortical atrophy independently affect cognition in CN older individuals.© 2015 American Academy of Neurology.

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