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Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
Published on: March 23, 2011
Hippocampal sclerosis in advanced age: clinical and pathological features
Peter T Nelson1, Frederick A Schmitt, Yushun Lin
1Department of Pathology, Division of Neuropathology and the Sanders-Brown Centre on Ageing, University of Kentucky, 800 S. Limestone, Lexington, KY 40536-0230, USA. pnels2@email.uky.edu
Brain : a Journal of Neurology
|May 21, 2011
Summary
Hippocampal sclerosis associated with ageing is common in the very old and linked to TAR DNA protein 43 pathology. A distinct cognitive profile may aid early clinical differentiation from Alzheimer's disease.
Area of Science:
- Neuropathology
- Gerontology
- Neuroscience
Background:
- Hippocampal sclerosis (HS) is a common finding in the elderly, distinct from Alzheimer's disease.
- Its association with aging (HS-A) and specific pathological markers remains under-investigated.
- Understanding HS-A is crucial for differentiating it from other neurodegenerative conditions.
Purpose of the Study:
- To characterize the neuropathological and clinical features of hippocampal sclerosis associated with ageing.
- To identify potential biomarkers for early clinical differentiation.
- To investigate the association between HS-A, TAR DNA protein 43 (TDP-43) pathology, and cognitive decline.
Main Methods:
- Combined three large autopsy cohorts (n=1110) for neuropathological evaluation.
- Focused on hippocampal sclerosis cases (n=106), particularly those aged ≥95 years.
- Utilized TAR DNA protein 43 immunohistochemistry and longitudinal cognitive assessments.
Main Results:
- Increased prevalence of HS-A with age beyond 95, inversely correlated with definite Alzheimer's disease.
- Aberrant TDP-43 immunohistochemistry found in 89.9% of HS cases, indicating bilateral pathology.
- A cognitive profile of high verbal fluency and low word list recall distinguished HS-A patients years before death.
Conclusions:
- HS-A is a distinct neuropathological entity in the aged brain, often associated with TDP-43 pathology.
- TDP-43 immunohistochemistry aids in diagnosing HS-A, even when gross pathology is subtle.
- Cognitive profiling offers a potential avenue for early clinical diagnosis of HS-A, differentiating it from Alzheimer's disease.
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