NIH: New Targets for Alzheimer's Treatment and Diagnosis

A recent study published in Nature Communications suggests that blood vessels called pericytes may provide novel targets for Alzheimer's disease treatments and diagnosis. 

Pericytes are cells that surround the outside of blood vessels. Many pericytes are found in the blood-brain barrier and control the movement of cells and molecules between the blood and interstitial fluid. 

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In this study, researchers show that pericytes may be a key to whether increased beta-amyloid leads to tangles and neuron loss.

Brains from Alzheimer's patients typically have abnormally high levels of beta-amyloid, neurofibrillary tangles inside neurons, and extensive neuron loss. In addition, previous research suggest that APOE4, a genetic risk factor for Alzheimer's disease, is linked to brain blood vessel health and integrity.

The study team crossbred mice genetically engineered to have a form of amyloid precursor protein (APP) linked to familial Alzheimer's with those that have reduced levels of platelet-derived growth factor beta receptor (PDGFR-beta). PDGFR-beta mutant mice have fewer pericytes, decreased brain blood flow, and a damaged blood-brain barrier.

Results showed that the APP and PDGFR-beta mutant mice had difficulty with learning and memory. Also, the mice had increased beta-amyloid plaque deposition near brain cells and along brain blood vessels. 

In the crossbred mice, enhanced neuronal cell death and extensive neurofibrillary tangles in the hippocampus and cerebral cortex were seen. The crossbred mutants also had more pericyte death and more damage to the blood-brain barrier than the PDGFR-beta mutant mice. 

The data confirmed previous findings that beta-amyloid accumulation leads to pericyte death.

Study authors concluded that the results supported their two-part hypothesis: the toxic effects of increased beta-amyloid deposition on pericytes in aged blood vessels leads to a breakdown of the blood-brain barrier and a reduced ability to clear amyloid from the brain. 

In turn, the progressive accumulation of beta-amyloid in the brain and death of pericytes may become a damaging feedback loop that causes dementia.

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