期刊
ACTA NEUROPATHOLOGICA COMMUNICATIONS
卷 10, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s40478-022-01471-z
关键词
Alzheimer's disease; Subtypes; Heterogeneity; Neuropathology; Neurofibrillary tangle; Positron emission tomography; Hippocampal sparing; Systematic review
资金
- Karolinska Institute
- Swedish Foundation for Strategic Research (SSF)
- Strategic Research Programme in Neuroscience at Karolinska Institutet (StratNeuro)
- Swedish Research Council
- Stockholm County Council
- Karolinska Institutet
- Center for Innovative Medicine (CIMED)
- Swedish Alzheimer Foundation
- Swedish Brain Foundation
- Ake Wiberg Foundation
- Demensfonden
- Neurofonden
- Stiftelsen Olle Engkvist Byggmastare
- Birgitta och Sten Westerberg
- National Institute on Aging [R01 AG054449, R01 AG075802, P30 AG062677, RF1 AG069052, U01 AG057195]
- Florida Department of Health, Ed and Ethel Moore Alzheimer's Disease Research Program [20A22]
This study examines different subtypes of Alzheimer's disease (AD) using neuropathology and neuroimaging techniques, and finds that tau PET can identify hippocampal sparing AD cases with neurofibrillary tangles (NFT) completely sparing the hippocampus.
Neuropathology and neuroimaging studies have identified several subtypes of Alzheimer's disease (AD): hippocampal sparing AD, typical AD, and limbic predominant AD. An unresolved question is whether hippocampal sparing AD cases can present with neurofibrillary tangles (NFT) in association cortices while completely sparing the hippocampus. To address that question, we conducted a systematic review and performed original analyses on tau positron emission tomography (PET) data. We searched EMBASE, PubMed, and Web of Science databases until October 2022. We also implemented several methods for AD subtyping on tau PET to identify hippocampal sparing AD cases. Our findings show that seven out of the eight reviewed neuropathologic studies included cases at Braak stages IV or higher and therefore, could not identify hippocampal sparing cases with NFT completely sparing the hippocampus. In contrast, tau PET did identify AD participants with tracer retention in the association cortex while completely sparing the hippocampus. We conclude that tau PET can identify hippocampal sparing AD cases with NFT completely sparing the hippocampus. Based on the accumulating data, we suggest two possible pathways of tau spread: (1) a canonical pathway with early involvement of transentorhinal cortex and subsequent involvement of limbic regions and association cortices, and (2) a less common pathway that affects association cortices with limbic involvement observed at end stages of the disease or not at all.
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