Harald Sontheimer, PhD, Awarded $3.5 Million to Study Memory Loss in Alzheimer’s Disease

June 11, 2024 by

Harald Sontheimer, PhD

Harald Sontheimer, PhD

Harald Sontheimer, PhD, a Harrison Distinguished Professor and chair of the Department of Neuroscience, was awarded a $3.5 million R01 grant from the National Institute for Aging for a project entitled “Extracellular matrix and memory impairments in Alzheimer’s disease.”

Alzheimer’s disease is a progressive neurodegenerative illness affecting over 5 million people in the U.S. and over 35 million worldwide. The disease is pathologically defined by the accumulation of protein aggregates called tau tangles and amyloid plaques believed to be involved in the progressive death of neurons, yet the cause of neuronal cell loss and associated dementia remains unclear.

As the leading cause for dementia, Alzheimer’s is invariably associated with profound memory loss, including recognition of close family members. Such memory, called social cognition memory, has been localized to a small brain region called the CA2 region of the hippocampus. In this region of the brain, neurons are encased by glycoproteins forming a web-like coat around neurons that was first described over 125 years ago by Camillo Golgi who named them perineuronal nets (PNNs).

In preliminary studies, the Sontheimer laboratory has shown in lab models of familial Alzheimer’s, PNNs are enzymatically degraded and that the resulting loss of PNNs in the CA2 is sufficient to cause impairments in social memory. Moreover, preventing loss of PNNs was found to delay memory impairments, providing a potential avenue to treat this form of memory loss in Alzheimer’s.

The proposed studies aim to define cellular and molecular changes that causally relate PNN degradation to progressive social memory impairments. If successful, these studies pave the way for the exploration of novel treatments of memory decline associated with Alzheimer’s.

Collaborators on the project include School of Medicine researchers Bhanu Tewari, PhD, Lata Chaunsali, MS, Ian Kimbrough, PhD, and Elise Cope, PhD.


Filed Under: Research