@article{1b19743a75d24bf3bbaec579b70c27b6,
title = "The hippocampal sparing subtype of Alzheimer{\textquoteright}s disease assessed in neuropathology and in vivo tau positron emission tomography: a systematic review",
abstract = "Neuropathology and neuroimaging studies have identified several subtypes of Alzheimer{\textquoteright}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.",
keywords = "Alzheimer{\textquoteright}s disease, Heterogeneity, Hippocampal sparing, Neurofibrillary tangle, Neuropathology, Positron emission tomography, Subtypes, Systematic review",
author = "Daniel Ferreira and Rosaleena Mohanty and Murray, {Melissa E.} and Agneta Nordberg and Kejal Kantarci and Eric Westman",
note = "Funding Information: MEM receives funding from the NIH, Alzheimer{\textquoteright}s Association, and the State of Florida; and has served as a paid consultant for AVID Radiopharmaceuticals. KK serves on the data safety monitoring board for Takeda Global Research and Development Center, Inc.; receives research support from Avid Radiopharmaceuticals and Eli Lilly, and receives funding from NIH and Alzheimer{\textquoteright}s Drug Discovery Foundation. DF, RM, AN, and EW declare that they have no competing interests. Funding Information: Open access funding provided by Karolinska Institute. This study was funded by the Swedish Foundation for Strategic Research (SSF); the Strategic Research Programme in Neuroscience at Karolinska Institutet (StratNeuro); the Swedish Research Council; the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet; Center for Innovative Medicine (CIMED); the Swedish Alzheimer Foundation; the Swedish Brain Foundation; the {\AA}ke Wiberg Foundation; Demensfonden; Neurofonden; Stiftelsen Olle Engkvist Byggm{\"a}stare; Birgitta och Sten Westerberg; National Institute on Aging (R01 AG054449, R01 AG075802, P30 AG062677, RF1 AG069052, U01 AG057195); and Florida Department of Health, Ed and Ethel Moore Alzheimer{\textquoteright}s Disease Research Program (20A22). The funding sources did not have any involvement on the study design; collection, analysis, and interpretation of data; writing of the report; and the decision to submit the article for publication. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1186/s40478-022-01471-z",
language = "English (US)",
volume = "10",
journal = "Acta neuropathologica communications",
issn = "2051-5960",
publisher = "BioMed Central",
number = "1",
}