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Entorhinal Tau Pathology, Episodic Memory Decline, and Neurodegeneration in Aging.
J Neurosci 2018; 38(3):530-543JN

Abstract

The medial temporal lobe (MTL) is an early site of tau accumulation and MTL dysfunction may underlie episodic-memory decline in aging and dementia. Postmortem data indicate that tau pathology in the transentorhinal cortex is common by age 60, whereas spread to neocortical regions and worsening of cognition is associated with β-amyloid (Aβ). We used [18F]AV-1451 and [11C]PiB positron emission tomography, structural MRI, and neuropsychological assessment to investigate how in vivo tau accumulation in temporal lobe regions, Aβ, and MTL atrophy contribute to episodic memory in cognitively normal older adults (n = 83; age, 77 ± 6 years; 58% female). Stepwise regressions identified tau in MTL regions known to be affected in old age as the best predictor of episodic-memory performance independent of Aβ status. There was no interactive effect of MTL tau with Aβ on memory. Higher MTL tau was related to higher age in the subjects without evidence of Aβ. Among temporal lobe subregions, episodic memory was most strongly related to tau-tracer uptake in the parahippocampal gyrus, particularly the posterior entorhinal cortex, which in our parcellation includes the transentorhinal cortex. In subjects with longitudinal MRI and cognitive data (n = 57), entorhinal atrophy mirrored patterns of tau pathology and their relationship with memory decline. Our data are consistent with neuropathological studies and further suggest that entorhinal tau pathology underlies memory decline in old age even without Aβ.SIGNIFICANCE STATEMENT Tau tangles and β-amyloid (Aβ) plaques are key lesions in Alzheimer's disease (AD) but both pathologies also occur in cognitively normal older people. Neuropathological data indicate that tau tangles in the medial temporal lobe (MTL) underlie episodic-memory impairments in AD dementia. However, it remains unclear whether MTL tau pathology also accounts for memory impairments often seen in elderly people and how Aβ affects this relationship. Using tau-specific and Aβ-specific positron emission tomography tracers, we show that in vivo MTL tau pathology is associated with episodic-memory performance and MTL atrophy in cognitively normal adults, independent of Aβ. Our data point to MTL tau pathology, particularly in the entorhinal cortex, as a substrate of age-related episodic-memory loss.

Authors+Show Affiliations

Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California 94720, anne.maass@dzne.de. German Center for Neurodegenerative Diseases, Magdeburg 39120, Germany.Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California 94720. Department of Internal Medicine, Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157.Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California 94720.Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California 94720.Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California 94720.Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California 94720.Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California 94720, and.Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California 94720. Memory and Aging Center, University of California San Francisco, San Francisco, California 94158.Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California 94720. Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California 94720, and.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29192126

Citation

Maass, Anne, et al. "Entorhinal Tau Pathology, Episodic Memory Decline, and Neurodegeneration in Aging." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 38, no. 3, 2018, pp. 530-543.
Maass A, Lockhart SN, Harrison TM, et al. Entorhinal Tau Pathology, Episodic Memory Decline, and Neurodegeneration in Aging. J Neurosci. 2018;38(3):530-543.
Maass, A., Lockhart, S. N., Harrison, T. M., Bell, R. K., Mellinger, T., Swinnerton, K., ... Jagust, W. J. (2018). Entorhinal Tau Pathology, Episodic Memory Decline, and Neurodegeneration in Aging. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 38(3), pp. 530-543. doi:10.1523/JNEUROSCI.2028-17.2017.
Maass A, et al. Entorhinal Tau Pathology, Episodic Memory Decline, and Neurodegeneration in Aging. J Neurosci. 2018 01 17;38(3):530-543. PubMed PMID: 29192126.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Entorhinal Tau Pathology, Episodic Memory Decline, and Neurodegeneration in Aging. AU - Maass,Anne, AU - Lockhart,Samuel N, AU - Harrison,Theresa M, AU - Bell,Rachel K, AU - Mellinger,Taylor, AU - Swinnerton,Kaitlin, AU - Baker,Suzanne L, AU - Rabinovici,Gil D, AU - Jagust,William J, Y1 - 2017/11/30/ PY - 2017/07/07/received PY - 2017/09/14/revised PY - 2017/10/07/accepted PY - 2017/12/2/pubmed PY - 2019/3/1/medline PY - 2017/12/2/entrez KW - aging KW - episodic memory KW - positron emission tomography KW - tau KW - transentorhinal cortex KW - β-amyloid SP - 530 EP - 543 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 38 IS - 3 N2 - The medial temporal lobe (MTL) is an early site of tau accumulation and MTL dysfunction may underlie episodic-memory decline in aging and dementia. Postmortem data indicate that tau pathology in the transentorhinal cortex is common by age 60, whereas spread to neocortical regions and worsening of cognition is associated with β-amyloid (Aβ). We used [18F]AV-1451 and [11C]PiB positron emission tomography, structural MRI, and neuropsychological assessment to investigate how in vivo tau accumulation in temporal lobe regions, Aβ, and MTL atrophy contribute to episodic memory in cognitively normal older adults (n = 83; age, 77 ± 6 years; 58% female). Stepwise regressions identified tau in MTL regions known to be affected in old age as the best predictor of episodic-memory performance independent of Aβ status. There was no interactive effect of MTL tau with Aβ on memory. Higher MTL tau was related to higher age in the subjects without evidence of Aβ. Among temporal lobe subregions, episodic memory was most strongly related to tau-tracer uptake in the parahippocampal gyrus, particularly the posterior entorhinal cortex, which in our parcellation includes the transentorhinal cortex. In subjects with longitudinal MRI and cognitive data (n = 57), entorhinal atrophy mirrored patterns of tau pathology and their relationship with memory decline. Our data are consistent with neuropathological studies and further suggest that entorhinal tau pathology underlies memory decline in old age even without Aβ.SIGNIFICANCE STATEMENT Tau tangles and β-amyloid (Aβ) plaques are key lesions in Alzheimer's disease (AD) but both pathologies also occur in cognitively normal older people. Neuropathological data indicate that tau tangles in the medial temporal lobe (MTL) underlie episodic-memory impairments in AD dementia. However, it remains unclear whether MTL tau pathology also accounts for memory impairments often seen in elderly people and how Aβ affects this relationship. Using tau-specific and Aβ-specific positron emission tomography tracers, we show that in vivo MTL tau pathology is associated with episodic-memory performance and MTL atrophy in cognitively normal adults, independent of Aβ. Our data point to MTL tau pathology, particularly in the entorhinal cortex, as a substrate of age-related episodic-memory loss. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/29192126/Entorhinal_Tau_Pathology_Episodic_Memory_Decline_and_Neurodegeneration_in_Aging_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=29192126 DB - PRIME DP - Unbound Medicine ER -