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Abstract

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. 

Author information

Brier MR1, Gordon B2, Friedrichsen K3, McCarthy J4, Stern A4, Christensen J3, Owen C3, Aldea P3, Su Y3, Hassenstab J5, Cairns NJ6, Holtzman DM7, Fagan AM7, Morris JC8, Benzinger TL9, Ances BM10.​

1Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, USA.

2Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, USA.

3Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA.

4Department of Mathematics, Washington University in St. Louis, St. Louis, MO 63110, USA.

5Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, USA.

6Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, USA. Department of Pathology, Washington University in St. Louis, St. Louis, MO 63110, USA.

7Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, USA. Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO 63110, USA.

8Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, USA. Department of Pathology, Washington University in St. Louis, St. Louis, MO 63110, USA. Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO 63110, USA.

9Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, USA. Department of Neurosurgery, Washington University in St. Louis, St. Louis, MO 63110, USA.

10Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, USA. Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, USA. Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO 63110, USA. bances@wustl.edu.