Multiple Neuropathologies Underly Hippocampal Subfield Atrophy in a Case With a Slowly Progressive Amnestic Syndrome: Challenging the Notion of Pure LATE-NC

被引：0

作者：

Youssef, Hossam ^{[1
]}

Gatto, Rodolfo G. ^{[1
]}

Pham, Nha Trang Thu ^{[2
]}

Jones, David ^{[1
]}

Petersen, Ronald C. ^{[1
]}

Machulda, Mary M. ^{[3
]}

Whitwell, Jennifer L. ^{[2
]}

Josephs, Keith A. ^{[1
]}

机构：

[1] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA

[2] Mayo Clin, Dept Radiol, Rochester, MN USA

[3] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA

来源：

NEUROPATHOLOGY | 2025年

关键词：

argyrophilic grain disease (AGD); limbic-predominant age-related TDP-43 encephalopathy-neuropathological change (LATE-NC); primary age-related tauopathy (PART); sequestosome-1/p62; transactive response DNA binding protein 43 (TDP-43); ARGYROPHILIC GRAIN DISEASE; ALZHEIMERS-DISEASE; TAU PATHOLOGY; CLINICAL-FEATURES; TDP-43; SEGMENTATION; ASSOCIATION; DEMENTIA; BRAIN; DEGENERATION;

D O I：

10.1111/neup.70000

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Alzheimer's disease (AD) is the leading cause of dementia in the elderly, marked by abnormal protein buildup (beta-amyloid and tau) resulting in neuronal loss, especially in the medial temporal lobe and other limbic regions. The presence of transactive response DNA binding protein 43 (TDP-43) immunoreactive inclusions in medial temporal lobe regions has also been associated with neuroimaging changes in limbic regions. It has been proposed that hypometabolism in limbic regions on [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) in a patient with a slowly evolving amnestic syndrome may be a signature of the presence of TDP-43. In this context, we observed an 86-year-old Caucasian female with dementia characterized by a slowly evolving amnestic syndrome, along with focal medial temporal atrophy evident on MRI and hypometabolism in limbic regions on FDG-PET. The patient subsequently died and underwent an autopsy. We performed detailed neuroimaging and digital neuropathological analyses of the hippocampal subfields to better understand the relationship between clinico-imaging findings and histopathology. In addition to TDP-43, we identified three other pathological processes in the medial temporal lobe: sequestosome-1/p62, argyrophilic grain disease (AGD), and primary age-related tauopathy (PART). Hippocampal subfield volumes and rates of atrophy were no different from those of matched healthy controls, except for the atrophy rate in cornu ammonis 1 (CA1). Digital histopathology revealed the relative highest burden of pathology for p62, followed by TDP-43, AGD, and PART in CA1. Multiple pathological processes appear to have contributed to the hippocampal atrophy and hypometabolism in our patient with a slowly progressive amnestic syndrome.

引用

页数：11