title: Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging.
abstract: Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Usingin vivohuman Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turn associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer's disease-related protein aggregation as an underlying mechanism of age-related memory impairment.SIGNIFICANCE STATEMENTAlterations in episodic memory and the accumulation of Alzheimer's pathology are common in cognitively normal older adults. However, evidence of pathological effects on episodic memory has largely been limited to β-amyloid (Aβ). Because Aβ and tau often cooccur in older adults, previous research offers an incomplete understanding of the relationship between pathology and episodic memory. With the recent development ofin vivotau PET radiotracers, we show that Aβ and tau are associated with different aspects of memory encoding, leading to aberrant neural activity that is behaviorally detrimental. In addition, our results provide evidence linking Aβ- and tau-associated neural dysfunction to brain atrophy.
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, and smmarks@berkeley.edu.
authors.forename: Shawn M
authors.identifier: 0000-0001-9884-8461
authors.initials: SM
authors.lastname: Marks
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, and.
authors.forename: Samuel N
authors.identifier: 0000-0002-0893-5420
authors.initials: SN
authors.lastname: Lockhart
authors.affiliation: Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California 94720.
authors.forename: Suzanne L
authors.identifier: 0000-0003-0209-3127
authors.initials: SL
authors.lastname: Baker
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, and.|Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California 94720.
authors.forename: William J
authors.identifier: 0000-0002-4458-113X
authors.initials: WJ
authors.lastname: Jagust
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology* / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D061212:Memory, Episodic; D008875:Middle Aged; D013702:Temporal Lobe / Q000033:anatomy & histology* / Q000502:physiology*; D055815:Young Adult; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; C054369:MAPT protein, human; D016875:tau Proteins
keywords: PET; amyloid; episodic memory; fMRI; hippocampus; tau