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Vascular pathology in familial Alzheimer disease

Date:
December 30, 2009
Source:
American Journal of Pathology
Summary:
New research demonstrates that presenilin-1 plays a role in the vascular pathology found in Alzheimer disease.
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A group led by Dr. Gregory A. Elder of the James J. Peters Veteran's Affairs Medical Center, Bronx, NY has demonstrated that presenilin-1 plays a role in the vascular pathology found in Alzheimer disease.

Their report can be found in the January 2010 issue of the American Journal of Pathology.

Alzheimer disease accounts for half of all dementias diagnosed each year. Mutations in presenilin-1 (PS-1), which cleaves amyloid precursor protein, are one of the most common causes of early onset cases of familial Alzheimer disease (FAD), which accounts for 5-10% of all Alzheimer disease sufferers.

Alzheimer disease is accompanied by vascular pathology, where blood vessels and microvessels are damaged. To determine if mutated PS-1 contributes to the vascular pathology observed in FAD, Gama Sosa et al generated a mouse model that overexpressed either wild-type or mutated human PS-1. They found age-related vascular pathology in these FAD model mice that was especially prominent in the microvasculature. However, the basis for this pathology appears to lie in the neurons, as neurons but not vascular endothelial or glial cells express PS-1 in these mice. Taken together, these results implicate a role for neuronal to vascular signaling in the pathogenesis of vascular pathology in FAD.

In future studies, Dr. Elder and colleagues plan to use their mouse model to "uncover the role of PS-1 FAD mutants in neurovascular signaling and provide insights into how neurovascular signaling may be disrupted in sporadic [Alzheimer disease] as well."


Story Source:

The above post is reprinted from materials provided by American Journal of Pathology. Note: Materials may be edited for content and length.


Journal Reference:

  1. Gama Sosa MA, De Gasperi R, Rocher AB, Wang AC-J, Janssen WGM, Flores T, Perez GM, Schmeidler J. Age-Related Vascular Pathology in Transgenic Mice Expressing Presenilin 1-Associated Familial Alzheimer's Disease Mutations. American Journal Of Pathology, 2010; 176 (1): 353 DOI: 10.2353/ajpath.2010.090482

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American Journal of Pathology. "Vascular pathology in familial Alzheimer disease." ScienceDaily. ScienceDaily, 30 December 2009. <www.sciencedaily.com/releases/2009/12/091230193104.htm>.
American Journal of Pathology. (2009, December 30). Vascular pathology in familial Alzheimer disease. ScienceDaily. Retrieved July 5, 2015 from www.sciencedaily.com/releases/2009/12/091230193104.htm
American Journal of Pathology. "Vascular pathology in familial Alzheimer disease." ScienceDaily. www.sciencedaily.com/releases/2009/12/091230193104.htm (accessed July 5, 2015).

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