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Heparan sulfate accumulation identified as “key initiating event” in Alzheimer’s could benefit Sanfilippo research

January 31, 2022
Molecular diagram of heparan sulfate a biomarker for Sanfilippo Syndrome

Thirty years ago, Alan Snow, PhD, and Thomas Wight, PhD,  hypothesized that heparan sulfate GAG accumulation and/or decreased heparan sulfate GAG degradation is the key initiating event in Alzheimer’s. This was a novel perspective of Alzheimer’s.

New studies and evidence have led Snow, a world-renowned expert in brain aging, memory loss, Alzheimer’s disease, Parkinson’s disease, and other amyloid disorders, to publish another article confirming the theory about the key role of heparan sulfate GAG accumulation and/or decreased heparan sulfate GAG degradation.

In the October 2021 publication, “The Unifying Hypothesis of Alzheimer’s Disease: Heparan Sulfate Proteoglycans/Glycosaminoglycans Are Key as First Hypothesized Over 30 Years Ago” in Frontiers in Aging Neuroscience, Snow, pointed out that, “Knockout of HS genes markedly reduce the accumulation of Aβ fibrils in the brain, demonstrating that HS GAGs are key [to Alzheimer’s].”

“New studies now implicate these macromolecules further and account for initiating events pertaining to AD pathology (plaques, tangles, cerebrovascular amyloid deposits); as well as unifying many different mechanisms that are all hypothesized to lead to AD and its pathology,” explains the publication. Snow also presents in the publication “an updated model for the specific roles of HSPGs and HS GAGs in initiation and progression of AD based on recent studies and data.”

The article is extensive and cites more than 175 research publications, including several regarding Sanfilippo. One of which was funded by Cure Sanfilippo Foundation.

“This research is important to Sanfilippo because Sanfilippo syndrome (MPS III) is also caused by the accumulation of heparan sulfate glycosaminoglycans,” said Cure Sanfilippo Foundation Chief Science Officer Cara O’Neill, MD, FAAP. “Because of this commonality, there is the potential for research regarding heparan sulfate GAG accumulation in Alzheimer’s to be relevant to Sanfilippo. And vice versa. It will be a space to continue watching.”

This page’s content summarizes basic information from the publication, “The Unifying Hypothesis of Alzheimer’s Disease: Heparan Sulfate Proteoglycans/Glycosaminoglycans Are Key as First Hypothesized Over 30 Years Ago” in Frontiers in Aging Neuroscience, October 2021, by Dr. Alan Snow.

 

 

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