Hippocampal sclerosis of aging (HS-A) is a type of age-related dementia characterized by neuronal loss and astrogliosis in the subiculum and CA1 subfield of the hippocampus, common amongst the oldest-old. HS-A mimics Alzheimer’s disease (AD) with similar symptomatic profiles. Despite its importance, relatively little is known about the disease and there are no biomarkers.

Figure 1. Hippocampal subfield, subregions, and measurements. a. Each hippocampal subfield was partitioned into thirds to determine the different subregions. The end closest to the entorhinal cortex was labeled as “A”, the end closest to CA4 was labeled as “C”, and the region in between A and C was labeled as “B”. b. For the quantitative measurements, the total length of each subfield (i.e., blue line for subiculum, yellow line for CA1, orange for CA2, and purple for CA3) was measured first. Then the length of the HS-A lesions was measured using the line annotation tool on Aperio eSlide Manager (dotted red lines). Using the total length of each subfield and subregion as denominator, we obtained ratios and reported the length of the HS-A lesions in proportions.

We have multiple projects investigating HS-A including our RO1 grant, where we will adopt a multi-faceted approach to enable diagnosis of this condition during life and to identify its risk factors. Related projects include identification of new neuropsychological tests that specifically rely on the neural substrate of hippocampal sclerosis i.e. CA1 region of hippocampus, and post mortem MRI project.