Tau and Aβ imaging, CSF measures, and cognition in Alzheimer's disease

• Published in: Science translational medicine Vol. 8; no. 338; p. 338ra66
• Main Authors: Brier, Matthew R, Gordon, Brian, Friedrichsen, Karl, McCarthy, John, Stern, Ari, Christensen, Jon, Owen, Christopher, Aldea, Patricia, Su, Yi, Hassenstab, Jason, Cairns, Nigel J, Holtzman, David M, Fagan, Anne M, Morris, John C, Benzinger, Tammie L S, Ances, Beau M
• Format: Journal Article
• Language: English
• Published: United States 11.05.2016
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - physiopathology; Amyloid beta-Peptides - cerebrospinal fluid; Amyloid beta-Peptides - metabolism; Brain - diagnostic imaging; Brain - metabolism; Cognition - physiology; Female; Humans; Male; Peptide Fragments - cerebrospinal fluid; Peptide Fragments - metabolism; Positron-Emission Tomography; tau Proteins - cerebrospinal fluid; tau Proteins - metabolism
• ISSN: 1946-6242
• DOI: 10.1126/scitranslmed.aaf2362

Alzheimer's disease (AD) is characterized by two molecular pathologies: cerebral β-amyloidosis in the form of β-amyloid (Aβ) plaques and tauopathy in the form of neurofibrillary tangles, neuritic plaques, and neuropil threads. Until recently, only Aβ could be studied in humans using positron emission tomography (PET) imaging owing to a lack of tau PET imaging agents. Clinical pathological studies have linked tau pathology closely to the onset and progression of cognitive symptoms in patients with AD. We report PET imaging of tau and Aβ in a cohort of cognitively normal older adults and those with mild AD. Multivariate analyses identified unique disease-related stereotypical spatial patterns (topographies) for deposition of tau and Aβ. These PET imaging tau and Aβ topographies were spatially distinct but correlated with disease progression. Cerebrospinal fluid measures of tau, often used to stage preclinical AD, correlated with tau deposition in the temporal lobe. Tau deposition in the temporal lobe more closely tracked dementia status and was a better predictor of cognitive performance than Aβ deposition in any region of the brain. These data support models of AD where tau pathology closely tracks changes in brain function that are responsible for the onset of early symptoms in AD.