Low-density lipoprotein receptor reduces damage in Alzheimer's brain

December 9, 2009

The low-density lipoprotein receptor (LDLR) has received a lot of attention because of its connection with coronary heart disease and atherosclerosis, but now it appears as if it may have a beneficial influence in degenerative brain diseases. New research, published by Cell Press in the December 10th issue of the journal Neuron, links LDLR with a reduction in brain changes associated with Alzheimer's disease (AD) and suggests a new therapeutic strategy for this incurable disease.

Amyloid beta-protein (Aβ) plays a major pathogenic role in AD, a devastating neurodegenerative disorder characterized by progressive cognitive impairment and memory loss. Accumulation of sticky extracellular Aβ plaques damages and is thought to play a central role in disease pathogenesis. Apolipoprotein E (apoE), an established genetic risk factor for late-onset AD, is involved in the metabolism and transport of fats, and previous work has implicated apoE in Aβ accumulation.

"Modulating the function of proteins that control apoE metabolism in the brain will likely alter the extent of amyloid deposition and ultimately affect the disease process," explains senior study author, Dr. David M. Holtzman from the Washington University School of Medicine. "We know that low-density lipoprotein (LDL) receptor binds to apoE, yet its potential role in AD pathogenesis remains unclear."

Dr. Holtzman and colleagues created transgenic mice that overexpressed LDLR in the brain and bred them with transgenic mice that were engineered to exhibit key pathological changes associated with AD, such as Aβ accumulation. Brain apoE levels were decreased by 50% to 90% in the LDLR and increased expression of LDLR-facilitated elimination of extracellular Aβ. Importantly, LDLR overexpression led to dramatic reductions in Aβ aggregation, amyloid plaque formation, and neuroinflammatory responses.

"Our study clearly demonstrates the beneficial effects of LDLR overexpression in the on pathogenic Aβ aggregation and subsequent neuroinflammatory responses," concludes Dr. Holtzman. "Given the results from these studies, the therapeutic potential of previously identified compounds, and potential new agents, which regulate LDLR in peripheral tissues merit additional testing in animal models of Aβ amyloidosis."

Source: Cell Press (news : web)

Explore further: Engineered mice provide insight into Alzheimer's disease

Related Stories

Engineered mice provide insight into Alzheimer's disease

January 17, 2008

One factor that determines how at risk an individual is of developing late-onset Alzheimer disease (AD) is the version of the APOE gene that they carry — those carrying the gene that enables them to make the apoE4 form ...

Novel role of protein in generating amyloid-beta peptide

April 27, 2009

A defining hallmark of Alzheimer's disease is the accumulation of the amyloid β protein (Aβ), otherwise known as "senile plaques," in the brain's cortex and hippocampus, where memory consolidation occurs. Researchers ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

(PhysOrg.com) -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.