TY - JOUR
T1 - APOE ε4 influences medial temporal atrophy and tau deposition in atypical Alzheimer's disease
AU - Singh, Neha Atulkumar
AU - Tosakulwong, Nirubol
AU - Graff-Radford, Jonathan
AU - Machulda, Mary M.
AU - Pham, Nha Trang Thu
AU - Sintini, Irene
AU - Weigand, Stephen D.
AU - Schwarz, Christopher G.
AU - Senjem, Matthew L.
AU - Carrasquillo, Minerva M.
AU - Ertekin-Taner, Nilufer
AU - Jack, Clifford R.
AU - Lowe, Val J.
AU - Josephs, Keith A.
AU - Whitwell, Jennifer L.
N1 - Funding Information:
The authors thank the patients and their families for their commitment. The authors especially thank AVID Radiopharmaceuticals for enabling the use of flortaucipir, their advice and oversight ,and for providing the necessary FDA regulatory cross‐filing permission and documentations. However, they were not involved in funding, or data analysis and interpretation. This study was funded by National Institutes of Health (grant numbers R01‐AG50603, R01‐DC010367, R01‐NS89757 and R01‐DC12519) and Alzheimer's Association (NIRG‐12‐242215). The sponsors played no role in the study design, data collection, analysis, interpretation, writing of the manuscript, or in the decision to submit the article for publication.
Funding Information:
The authors thank the patients and their families for their commitment. The authors especially thank AVID Radiopharmaceuticals for enabling the use of flortaucipir, their advice and oversight, and for providing the necessary FDA regulatory cross-filing permission and documentations. However, they were not involved in funding, or data analysis and interpretation. This study was funded by National Institutes of Health (grant numbers R01-AG50603, R01-DC010367, R01-NS89757 and R01-DC12519) and Alzheimer's Association (NIRG-12-242215). The sponsors played no role in the study design, data collection, analysis, interpretation, writing of the manuscript, or in the decision to submit the article for publication.
Funding Information:
NAS, IS, MMC, ET, NTTP, NT, and SW have no disclosures to report. JW, GR, MM, CGS and KAJ reported receiving research funding from the NIH. MS reported holding stock in Gilead Sciences, Inc., Inovio Pharmaceuticals, Medtronic, Oncothyreon, Inc., and PAREXEL International. CRJ reported serving on an independent data monitoring board for Roche, has consulted for and served as a speaker for Eisai, and consulted for Biogen, but he receives no personal compensation from any commercial entity. He receives research support from NIH and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic. VJL reported consulting for Bayer Schering Pharma, Piramal Life Sciences, Life Molecular Imaging, Eisai Inc., AVID Radiopharmaceuticals, and Merck Research and receiving research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals and the NIH (NIA, NCI). The other authors declare that they have no competing financial interests. Author disclosures are available in the supporting information.
Publisher Copyright:
© 2022 the Alzheimer's Association.
PY - 2023/3
Y1 - 2023/3
N2 - Introduction: Apolipoprotein E (APOE) ε4 is an important genetic risk factor for typical Alzheimer's disease (AD), influencing brain volume and tau burden. Little is known about its influence in atypical presentations of AD. Methods: An atypical AD cohort of 140 patients diagnosed with either posterior cortical atrophy or logopenic progressive aphasia underwent magnetic resonance imaging and positron emission tomography. Linear mixed effects models were fit to assess the influence of APOE ε4 on cross-sectional and longitudinal regional metrics. Results: At baseline, APOE ε4 carriers had smaller hippocampal and amygdala volumes and greater tau standardized uptake volume ratio in the hippocampus and entorhinal cortex compared to non-carriers while longitudinally, APOE ε4 non-carriers showed faster rates of atrophy and tau accumulation in the entorhinal cortex, with faster tau accumulation in the hippocampus. Discussion: APOE ε4 influences patterns of neurodegeneration and tau deposition and was associated with more medial temporal involvement, although there is evidence that non-carriers may be catching up over time.
AB - Introduction: Apolipoprotein E (APOE) ε4 is an important genetic risk factor for typical Alzheimer's disease (AD), influencing brain volume and tau burden. Little is known about its influence in atypical presentations of AD. Methods: An atypical AD cohort of 140 patients diagnosed with either posterior cortical atrophy or logopenic progressive aphasia underwent magnetic resonance imaging and positron emission tomography. Linear mixed effects models were fit to assess the influence of APOE ε4 on cross-sectional and longitudinal regional metrics. Results: At baseline, APOE ε4 carriers had smaller hippocampal and amygdala volumes and greater tau standardized uptake volume ratio in the hippocampus and entorhinal cortex compared to non-carriers while longitudinally, APOE ε4 non-carriers showed faster rates of atrophy and tau accumulation in the entorhinal cortex, with faster tau accumulation in the hippocampus. Discussion: APOE ε4 influences patterns of neurodegeneration and tau deposition and was associated with more medial temporal involvement, although there is evidence that non-carriers may be catching up over time.
KW - apolipoprotein ε4
KW - atypical Alzheimer's disease
KW - logopenic progressive aphasia
KW - magnetic resonance imaging
KW - posterior cortical atrophy
KW - tau positron emission tomography
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U2 - 10.1002/alz.12711
DO - 10.1002/alz.12711
M3 - Article
C2 - 35691047
AN - SCOPUS:85131551197
SN - 1552-5260
VL - 19
SP - 784
EP - 796
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 3
ER -