RT Journal Article
T1 Antemortem basal forebrain atrophy in pure limbic TAR DNA-binding protein 43 pathology compared with pure Alzheimer pathology.
A1 Teipel, Stefan J
A1 Grothe, Michel J
K1 AD pathology
K1 MRI
K1 autopsy
K1 cholinergic deficit
K1 imaging signature
K1 limbic TDP-43
AB Currently, the extent of cholinergic basal forebrain atrophy in relatively pure limbic TAR DNA-binding protein 43 (TDP-43) pathology compared with relatively pure Alzheimer disease (AD) is unclear. We compared antemortem magnetic resonance imaging (MRI)-based atrophy of the basal forebrain and medial and lateral temporal lobe volumes between 10 autopsy cases with limbic TDP-43 pathology and 33 cases with AD pathology on postmortem neuropathologic examination from the Alzheimer's Disease Neuroimaging Initiative cohort. For reference, we studied MRI volumes from cognitively healthy, amyloid positron emission tomography-negative subjects (n = 145). Group differences were assessed using Bayesian analysis of covariance. In addition, we assessed brain-wide regional volume changes using partial least squares regression (PLSR). We found extreme evidence (Bayes factor [BF]01  > 600) for a smaller basal forebrain volume in both TDP-43 and AD cases compared with amyloid-negative controls, and moderate evidence (BF01  = 4.9) that basal forebrain volume was not larger in TDP-43 than in AD cases. The ratio of hippocampus to lateral temporal lobe volumes discriminated between TDP-43 and AD cases with an accuracy of 0.78. PLSR showed higher gray matter in lateral temporal lobes and cingulate and precuneus, and reduced gray matter in precentral and postcentral gyri and hippocampus in TDP-43 compared with AD cases. Atrophy of the cholinergic basal forebrain appears to be similarly pronounced in cases with limbic TDP-43 pathology as in AD. This suggests that a clinical trial of the efficacy of cholinesterase inhibitors in amyloid-negative cases with amnestic dementia and an imaging signature of TDP-43 pathology may be warranted.
PB Wiley-Blackwell Publishing Ltd.
SN 1351-5101
YR 2022
FD 2022-02-19
LK http://hdl.handle.net/10668/19950
UL http://hdl.handle.net/10668/19950
LA en
NO Teipel SJ, Grothe MJ; Alzheimer's Disease Neuroimaging Initiative. Antemortem basal forebrain atrophy in pure limbic TAR DNA-binding protein 43 pathology compared with pure Alzheimer pathology. Eur J Neurol. 2022 May;29(5):1394-1401.
NO Data collection and sharing for this project were funded by the ADNI (National Institutes of Health grant U01 AG024904) and Department of Defense (DOD) ADNI (DOD award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging and the National Institute of  Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Araclon Biotech, BioClinica, Biogen Idec, Bristol-Myers Squibb, Eisai, Elan Pharmaceuticals, Eli Lilly and Company, EuroImmun, F. Hoffmann-La Roche and its affiliated company Genentech, Fujirebio, GE Healthcare, IXICO, Janssen Alzheimer Immunotherapy Research & Development, Johnson & Johnson Pharmaceutical Research & Development, Medpace, Merck & Co, Meso Scale Diagnostics, NeuroRx Research, Neurotrack Technologies, Novartis Pharmaceuticals Corporation, Pfizer, Piramal Imaging, Servier, Synarc, and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. The work was supported by a grant to S.J.T. within the CureDem funding of the Federal Ministry of Research (grant number 01KX2130). M.J.G. is supported by the Miguel Servet program (CP19/00031) and a research grant (PI20/00613) of the Carlos III Health Institute–European Regional Development Fund. Open Access funding enabled and organized by Projekt DEAL.
DS RISalud
RD Apr 10, 2025