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J Neuropathol Exp Neurol. 2015 Jul;74(7):642-52. doi: 10.1097/NEN.0000000000000204.

Hippocampal Sclerosis of Aging Can Be Segmental: Two Cases and Review of the Literature.

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From Department of Pathology, Division of Neuropathology (JHN, PTN), Department of Neurology (GAJ, FAS, CDS), Department of Statistics (RJK), Department of Epidemiology (ELA), Sanders-Brown Center on Aging (GAJ, FAS, ELA, RJK, CDS, TD, SA, EL, AB, LVE, PTN), and Department of Anatomy and Neurobiology (ETI, LVE, PTN), University of Kentucky, Lexington, Kentucky.


Hippocampal sclerosis of aging (HS-Aging) is a neurodegenerative disease that mimics Alzheimer disease (AD) clinically and has a prevalence rivaling AD in advanced age. Whereas clinical biomarkers are not yet optimized, HS-Aging has distinctive pathological features that distinguish it from other diseases with "hippocampal sclerosis" pathology, such as epilepsy, cerebrovascular perturbations, and frontotemporal lobar degeneration. By definition, HS-Aging brains show neuronal cell loss and gliosis in the hippocampal formation out of proportion to AD-type pathology; it is strongly associated with aberrant TDP-43 pathology and arteriolosclerosis. Here, we describe 2 cases of "segmental" HS-Aging in which "sclerosis" in the hippocampus was evident only in a subset of brain sections by hematoxylin and eosin (H&E) stain. In these cases, TDP-43 pathology was more widespread on immunostained sections than the neuronal cell loss and gliosis seen in H&E stains. The 2 patients were cognitively intact at baseline and were tracked longitudinally over a decade using cognitive studies with at least 1 neuroimaging scan. We discuss the relevant HS-Aging literature, which indicates the need for a clearer consensus-based delineation of "hippocampal sclerosis" and TDP-43 pathologies in aged subjects.

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