Article
Clinical Neurology
Sonal Agrawal, Lei Yu, Alifiya Kapasi, Bryan D. James, Konstantinos Arfanakis, Lisa L. Barnes, David A. Bennett, Sukriti Nag, Julie A. Schneider
Summary: The study found that LATE-NC is commonly associated with microvascular pathologies, particularly posterior watershed arteriolosclerosis. This suggests that small vessel disease pathology may play a role in the development of LATE-NC in the aging brain.
Article
Clinical Neurology
Maiko T. Uemura, John L. Robinson, Katheryn A. Q. Cousins, Thomas F. Tropea, Daniel C. Kargilis, Jennifer D. McBride, EunRan Suh, Sharon X. Xie, Yan Xu, Silvia Porta, Norihito Uemura, Vivianna M. Van Deerlin, David A. Wolk, David J. Irwin, Kurt R. Brunden, Virginia M. -Y. Lee, Edward B. Lee, John Q. Trojanowski
Summary: Limbic-predominant age-related TDP-43 encephalopathy (LATE) is characterized by the accumulation of TAR-DNA-binding protein 43 (TDP-43) aggregates in older adults and coexists with Lewy body disease (LBD) and Alzheimer's disease (AD). Pathological and genetic characteristics of LATE in LBD (LATE-LBD) differ from LATE-AD, with associations to patient profiles and cognitive impairment. The distribution of LATE neuropathological changes and genetic risk factors also vary between LATE-LBD and LATE-AD.
ACTA NEUROPATHOLOGICA
(2022)
Article
Neurosciences
Sonal Agrawal, Lei Yu, Sukriti Nag, Konstantinos Arfanakis, Lisa L. Barnes, David A. Bennett, Julie A. Schneider
Summary: LBs and LATE-NC are common in older individuals and linked to cognitive impairment. The combination of LBs and LATE-NC may affect cognition and Alzheimer's dementia in community-dwelling participants. Neocortical-type LBs are associated with LATE-NC, particularly in younger old individuals and women, and have separate and additive effects on cognitive function and odds of Alzheimer's dementia.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Clinical Neurology
Aya Murakami, Shunsuke Koga, Hiroaki Sekiya, Bjorn Oskarsson, Kevin Boylan, Leonard Petrucelli, Keith A. Josephs, Dennis W. Dickson
Summary: This study aimed to assess and compare the burden of transactive response DNA-binding protein of 43 kDa (TDP-43) pathology and clinical features of amyotrophic lateral sclerosis (ALS) in three age groups. The study found that the amygdala and hippocampus are vulnerable to TDP-43 pathology in older patients with ALS.
Article
Clinical Neurology
Kathryn Gauthreaux, Charles Mock, Merilee A. Teylan, Jessica E. Culhane, Yen-Chi Chen, Kwun C. G. Chan, Yuriko Katsumata, Peter T. Nelson, Walter A. Kukull
Summary: Transactive response DNA-binding protein 43 kDa (TDP-43) proteinopathy, the hallmark of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), commonly coexists with Alzheimer disease neuropathologic change (ADNC). This study compared the clinical features and copathologies of autopsy-confirmed ADNC with and without comorbid LATE-NC. The results showed that LATE-NC was associated with more severe ADNC, hippocampal sclerosis, and brain arteriolosclerosis copathologies. Participants with comorbid LATE-NC had higher ADNC burden and worse cognitive performance, particularly in those with low/intermediate ADNC burden.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2022)
Article
Geriatrics & Gerontology
Mahir Tazwar, Arnold M. Evia, Ashish A. Tamhane, Abdur Raquib Ridwan, Sue E. Leurgans, David A. Bennett, Julie A. Schneider, Konstantinos Arfanakis
Summary: This study found an association between limbic predominant age-related transactive response DNA binding protein 43 (TDP-43) encephalopathy neuropathological change (LATE-NC) and the transverse relaxation rate R-2. R-2 imaging can capture the progression of LATE-NC, and the spatial pattern of lower R-2 is consistent with the distribution of LATE-NC in the brain.
NEUROBIOLOGY OF AGING
(2022)
Review
Clinical Neurology
Michael Tran Duong, David A. Wolk
Summary: Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a neurodegenerative disease that is distinct from other cognitive disorders and commonly coexists with Alzheimer's disease and cerebrovascular disease. Researchers are developing novel biomarkers to diagnose LATE.
CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
(2022)
Article
Clinical Neurology
Heather Maioli, Rhonda Mittenzwei, Jane B. Shofer, Kathryn P. Scherpelz, Desiree Marshall, Amber L. Nolan, Peter T. Nelson, C. Dirk Keene, Caitlin S. Latimer
Summary: LATE-NC, a proteinopathy associated with cognitive impairment in the elderly population, can be effectively distinguished using a condensed protocol (CP) that utilizes a single tissue block and immunostain. This study demonstrates the CP's ability to discriminate between different stages of LATE-NC, making it applicable in clinical practice.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Article
Geriatrics & Gerontology
Morgane Darricau, Marie-Helene Canron, Marion Bosc, Marie-Laure Arotcarena, Megane Le Quang, Benjamin Dehay, Erwan Bezard, Vincent Planche
Summary: Through studying the brain tissues of aged rhesus macaques, it was found that LATE may be a human-specific condition and does not contribute to age-related memory impairment in non-human primates.
NEUROBIOLOGY OF AGING
(2021)
Article
Clinical Neurology
Marina Buciuc, Jennifer L. Whitwell, Matthew C. Baker, Rosa Rademakers, Dennis W. Dickson, Keith A. Josephs
Summary: The burden of TDP-43 inclusions was assessed in elderly patients with genetic FTLD-TDP and compared to sporadic cases with TDP-43. It was found that patients with genetic FTLD-TDP had a higher burden in the entorhinal cortex compared to AD-TDP, but no significant difference in the middle frontal cortex burden.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Neurosciences
Stefan Teipel, Michel J. Grothe
Summary: This study aims to investigate the association between limbic TDP-43 pathology and cholinergic deficit in the absence of Alzheimer's disease (AD) pathology, and evaluate MRI-based patterns of atrophy as a surrogate marker for TDP-43. The results showed that there was a comparable degree of basal forebrain atrophy in pure TDP-43 cases compared to AD cases, which encourages further studies on cholinergic treatment in amnestic dementia due to TDP-43. Moreover, a distinct pattern of temporo-limbic brain atrophy may serve as a surrogate marker to enrich samples in clinical trials for the presence of TDP-43 pathology.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Clinical Neurology
Stefan J. Teipel, Michel J. Grothe
Summary: This study compared the atrophy of the cholinergic basal forebrain in cases with limbic TDP-43 pathology and pure Alzheimer disease (AD) using MRI. The findings suggest that the atrophy of the cholinergic basal forebrain is similarly pronounced in both TDP-43 and AD cases, indicating a potential need for clinical trials of cholinesterase inhibitors in amyloid-negative cases with amnestic dementia and an imaging signature of TDP-43 pathology.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Alexandra L. Young, Jacob W. Vogel, John L. Robinson, Corey T. McMillan, Rik Ossenkoppele, David A. Wolk, David J. Irwin, Lauren Elman, Murray Grossman, Virginia M. Y. Lee, Edward B. Lee, Oskar Hansson
Summary: Through data-driven disease progression modelling, a fine-grained empirical staging system for TAR DNA-binding protein-43 (TDP-43) proteinopathies has been established, which can accurately classify frontotemporal lobar degeneration due to TDP-43 (FTLD-TDP), amyotrophic lateral sclerosis (ALS) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). The study reveals substantial heterogeneity in the progression patterns of ALS and FTLD-TDP, and highlights the need for further investigation in larger cross-cohort studies.
Article
Clinical Neurology
Arenn F. F. Carlos, Nirubol Tosakulwong, Stephen D. D. Weigand, Matthew L. L. Senjem, Christopher G. G. Schwarz, David S. S. Knopman, Bradley F. F. Boeve, Ronald C. C. Petersen, Aivi T. T. Nguyen, R. Ross Reichard, Dennis W. W. Dickson, Clifford R. R. Jack Jr, Val Lowe, Jennifer L. L. Whitwell, Keith A. A. Josephs
Summary: This study investigated the impact of age and TDP-43 pathology on the volume-uptake mismatch in older Alzheimer's disease patients. The results showed that TDP-43 pathology was associated with reduced medial temporal volumes but not with F-18-flortaucipir uptake. The effect size of TDP-43 pathology remained consistent across the age spectrum, but in older age, the mean volumes moved towards those of TDP-43-positive cases, reflecting the increasing frequency of TDP-43 pathology with age.
ALZHEIMERS & DEMENTIA
(2022)
Article
Clinical Neurology
Shahram Oveisgharan, Lei Yu, Sonal Agrawal, Sukriti Nag, David A. Bennett, Aron S. Buchman, Julie A. Schneider
Summary: LATE-NC is associated with declining motor function in older adults.