Alzheimer's disease might be a 'whole body' problem

Alzheimer's disease, the leading cause of dementia, has long been assumed to originate in the brain. But research from the University of British Columbia and Chinese scientists indicates that it could be triggered by breakdowns elsewhere in the body. The findings, published today in Molecular Psychiatry, offer hope that future drug therapies might be able to stop or slow the disease without acting directly on the brain, which is a complex, sensitive and often hard-to-reach target. Instead, such drugs could target the kidney or liver, ridding the blood of a toxic protein before it ever reaches the brain.

The scientists demonstrated this cancer-like mobility through a technique called parabiosis: surgically attaching two specimens together so they share the same blood supply for several months.

UBC Psychiatry Professor Dr. Weihong Song and Neurology Professor Yan-Jiang Wang at Third Military Medical University in Chongqing attached normal mice, which don't naturally develop Alzheimer's disease, to mice modified to carry a mutant human gene that produces high levels of a protein called amyloid-beta. In people with Alzheimer's disease, that protein ultimately forms clumps, or "plaques," that smother brain cells.

Normal mice that had been joined to genetically modified partners for a year "contracted" Alzheimer's disease. Song says the amyloid-beta traveled from the genetically-modified mice to the brains of their normal partners, where it accumulated and began to inflict damage.

Not only did the normal mice develop plaques, but also a pathology similar to "tangles" - twisted protein strands that form inside brain cells, disrupting their function and eventually killing them from the inside-out. Other signs of Alzheimer's-like damage included brain cell degeneration, inflammation and microbleeds. In addition, the ability to transmit electrical signals involved in learning and memory - a sign of a healthy brain - was impaired, even in mice that had been joined for just four months.

Besides the brain, amyloid-beta is produced in blood platelets, blood vessels and muscles, and its precursor protein is found in several other organs. But until these experiments, it was unclear if amyloid-beta from outside the brain could contribute to Alzheimer's disease. This study, Song says, shows it can.

"The blood-brain barrier weakens as we age," says Song, a Canada Research Chair in Alzheimer's Disease and the Jack Brown and Family Professor. "That might allow more amyloid beta to infiltrate the brain, supplementing what is produced by the brain itself and accelerating the deterioration."

Song, head of UBC's Townsend Family Laboratories, envisions a drug that would bind to amyloid-beta throughout the body, tagging it biochemically in such a way that the liver or kidneys could clear it.

"Alzheimer's disease is clearly a disease of the brain, but we need to pay attention to the whole body to understand where it comes from, and how to stop it," he says.

XL Bu, Y Xiang, WS Jin, J Wang, LL Shen, ZL Huang, K Zhang, YH Liu, F Zeng, JH Liu, HL Sun, ZQ Zhuang, SH Chen, XQ Yao, B Giunta, YC Shan, J Tan, XW Chen, ZF Dong, HD Zhou, XF Zhou, W Song, YJ Wang.
Blood-derived amyloid-β protein induces Alzheimer’s disease pathologies.
Molecular Psychiatry. doi: 10.1038/mp.2017.204.

Most Popular Now

Delivering insulin in a pill

Given the choice of taking a pill or injecting oneself with a needle, most of us would opt to regulate a chronic health condition by swallowing a pill. But for millions o...

Can aspirin treat Alzheimer's?

A regimen of low-dose aspirin potentially may reduce plaques in the brain, which will reduce Alzheimer's disease pathology and protect memory, according to neurological r...

Probiotics can protect the skeletons of older wome…

For the first time in the world, researchers at the University of Gothenburg, Sweden, have demonstrated that probiotics, dietary supplements with health-promoting bacteri...

Alzheimer's breakthrough: Brain metals that may dr…

Alzheimer's disease could be better treated, thanks to a breakthrough discovery of the properties of the metals in the brain involved in the progression of the neurodegen...

FDA approves first drug comprised of an active ing…

The U.S. Food and Drug Administration today approved Epidiolex (cannabidiol) [CBD] oral solution for the treatment of seizures associated with two rare and severe forms o...

Researchers develop a new method for turning skin …

Our bodies consist of many different kinds of cells, each with their own role. The Japanese scientist Shinya Yamanaka had made earlier the discovery, earning the Nobel Pr...

Some existing anti-cancer drugs may act in part by…

Bolstering the notion that RNA should be considered an important drug-discovery target, scientists at Scripps Research have found that several existing, FDA-approved anti...

FDA takes steps to foster greater efficiency in bi…

Today, the agency withdrew the draft guidance, "Statistical Approaches to Evaluate Analytical Similarity," issued in September 2017. The draft guidance, if finalized as w...

Poliovirus therapy for recurrent glioblastoma has …

A genetically modified poliovirus therapy developed at Duke Cancer Institute shows significantly improved long-term survival for patients with recurrent glioblastoma, wit...

Novartis Clear about Psoriasis survey data highlig…

Novartis announced today the publication of global Clear about Psoriasis survey data in the Journal of the European Academy of Dermatology and Venereology[1]. The publica...

How targeting metabolism can defeat cancer stem ce…

Researchers are the University of Michigan Rogel Cancer are unraveling a crucial thread that explains why cancer so often becomes resistant to treatment. In a breakthroug...

New small molecules pave the way for treating auto…

The innate immune system is the first line of defense, with cells that quickly identify "foreign" motifs from viruses and bacteria and mount up a counterattack to elimina...