Visualizing the Impacts of Age and Disease on the Brain

By Fatin Chowdhury ‘19

Figure 1. Computational methods can be used to explore the effects of neurodegenerative disease and aging on the hippocampus.

Alzheimer’s disease (AD), a common neurodegenerative disorder, has previously been found to increase atrophy rate of the hippocampus, an area of the brain associated with learning and memory. In relation to this issue, Dr. Daniel H. Adler and researchers from the University of Pennsylvania recently examined specific structural details of the human hippocampus as relevant to advanced age and AD.

Thirty-one ex vivo human hippocampal specimens were examined in 10% formalin solution and imaged on a Varian animal scanner. The researchers constructed a visual 3D atlas of these specimens, via MRIs, histological study, and application of algorithms. Segments of hippocampal and myelinated SRLM (strata radiatum, lacunosum, and molecular) layer regions were semi manually produced. Nine specimens were histologically analyzed as one-centimeter thick blocks, thin sliced using a vibratome, and situated in paraffin.

Utilizing linear modeling in their measurements and data analysis of the brain, the researchers produced the atlas, which depicted probabilistic morphology changes occurring with Alzheimer’s disease and allowed for examination of brain region shapes. The study indicated that hippocampus volume decreased 2% with each added year of age. The researchers uncovered a link between dentate gyrus shrinking and the subject’s age, as the area decreased 3.3% in size per year, while the cornu ammonis region decreased 2.5% per year. The researchers acknowledged limitations inherent in the study, such as how only nine specimens could undergo histological processing due to necessary resources. Despite such limitations, the informative nature of the 3D atlas indicates that ex vivo histology and MRI can be used as complementary tools for analyzing the anatomical changes accompanying neurodegenerative diseases.


  1. N. Schuff et al., MRI of hippocampal volume loss in early Alzheimer’s disease in relation to ApoE genotype and biomarkers. Brain 132, 1067-1077 (2009). doi: 10.1093/brain/awp007.
  2. D. Adler et al., Characterizing the human hippocampus in aging and Alzheimer’s disease using a computational atlas derived from ex vivo MRI and histology. Proceedings of the National Academy of Sciences 115, 4252-4257 (2018). doi:10.1073/pnas.1801093115
  3. Image retrieved from:

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