Potential therapy removes APOE and plaques from brain
Years before people start showing characteristic symptoms of Alzheimer’s disease, sticky plaques begin forming in their brains, damaging nearby cells. For decades, doctors have sought ways to clear out these plaques as a way to prevent or treat the disease.
The sticky clumps, known as amyloid plaques, are composed primarily of a brain protein called amyloid beta. But nestled within the plaques are small amounts of another Alzheimer’s protein: APOE. Now, researchers at Washington University School of Medicine have shown that an antibody not only targets APOE for removal but sweeps away plaques.
The findings, available March 26 in the Journal of Clinical Investigation, could lead to a way to halt the brain damage triggered by amyloid plaques while the disease is still in its early stages, perhaps before symptoms appear.
“Many people build up amyloid over many years, and the brain just can’t get rid of it,” said senior author David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. “By removing plaques, if we start early enough, we may be able to stop the changes to the brain that result in forgetfulness, confusion and cognitive decline.”
Variants of the gene APOE are the single largest risk factor for Alzheimer’s disease. In earlier work, Holtzman and colleagues have shown that a DNA-based compound that targets APOE can lessen the injury caused by amyloid plaques.
But getting rid of the plaques likely would protect the brain better than blunting the plaques’ destructiveness. To find out whether the plaques could be removed, Holtzman, co-first authors Fan Liao, PhD, a postdoctoral researcher, and Aimin Li, PhD, a senior scientist, and colleagues focused on antibodies that recognize and bind to APOE. Once antibodies attach themselves to their APOE target, they attract the attention of roving immune cells, which carry both antibody and target off to be destroyed. The researchers reasoned that nearby amyloid might be cleared away along with APOE.
The researchers tested several antibodies that recognize human APOE in mice genetically predisposed to develop amyloid plaques. The APOE genes of the mice had been replaced with a human APOE gene. The antibodies were developed in collaboration with Denali Therapeutics.
For six weeks, the mice were given weekly injections of placebo or antibodies against APOE. Then, the researchers measured the amount of plaques in their brains. One antibody – called HAE-4 – cut the level of plaques by half.
Moreover, HAE-4 had no effect on APOE levels in the blood. APOE plays an important role in transporting fats and cholesterol in the body, so removing it from the bloodstream could create unwanted side effects. The failure of the antibody to lower levels of APOE in the blood was therefore a good sign. But it was also a mystery. Why did the antibody clear APOE from the brain but not the blood?
“It turns out that the APOE in the plaques has a different structure than the form of APOE found in the blood,” Holtzman said. “The HAE-4 antibody recognized only the form found attached to the plaques in the brain.”
No treatment exists to prevent or delay onset – or slow the trajectory – of Alzheimer’s disease. But a few antibodies that clear plaques by targeting amyloid beta are being evaluated in clinical trials. While such antibodies are promising, they sometimes come with the side effect of inflammation and swelling in the brain.
However, antibodies that target APOE may be successful at removing plaques in people and somewhat less likely to trigger a destructive immune response, Holtzman said.
“The anti-amyloid antibodies are going to be binding to most of the molecules that are in the plaque, but the anti-APOE antibody would target just a very small component of the plaque,” Holtzman said. “This means we may find less immune activation, and we might not see the unwelcome side effects.”
The researchers are planning further studies to determine whether similar antibodies are safe and might be effective enough to be used in people.
The Latest on: Alzheimer’s plaques
via Google News
The Latest on: Alzheimer’s plaques
- New study finds ultrasound stimulation as effective therapy for Alzheimer's diseaseon January 26, 2022 at 12:51 pm
Alzheimer's disease (AD), is one of them, being extremely prevalent within ageing societies in Japan, Korea, and various European countries. Currently, there is no cure or an effective strategy to ...
- New Ultrasound Stimulation an Effective Therapy for Alzheimer’son January 25, 2022 at 7:08 pm
Alzheimer's disease affects over 50 million people worldwide and is presently incurable. A viable treatment strategy involves reducing abnormal protein accumulation in the brain with gamma waves.
- Wash. U lands major grant in battle against Alzheimer’son January 25, 2022 at 3:00 pm
The Alzheimer’s Association, with GHR Foundation and Edward Jones, announced a $14 million commitment in support of Washington University’s Dominantly Inherited Alzheimer’s Network Trials Unit ...
- An Alternative Hypothesis of Alzheimer’s Based on Synaptic Alterationson January 25, 2022 at 2:27 pm
Amyloid precursor protein accumulated with an excess of presynaptic proteins, whereas post synaptic proteins were depleted.
- Alzheimer's disease: An alternative hypothesis based on synaptic alterationson January 25, 2022 at 7:14 am
New research published today in Alzheimer's & Dementia, the journal of the Alzheimer's Association could explain why neurons fail to communicate effectively in people with Alzheimer's disease (AD).
- Two small biotechs hope that gene therapy will be the future of Alzheimer’s disease treatment. Here’s what we know so far.on January 25, 2022 at 5:30 am
Biotechs Lexeo Therapeutics and Shape Therapeutics gave the public its first look at the one-and-done gene therapies they're creating for Alzheimer's.
- Making sense of controversy over the new Alzheimer’s drugon January 24, 2022 at 2:50 pm
The medication has shown some promise at addressing what may be an underlying cause of the disease, but its ability to slow or reverse cognitive decline remains unproven.
- Rapid amyloid PET scans show promise in Alzheimer's diseaseon January 23, 2022 at 11:37 pm
Amyloid PET imaging performed in just a few minutes appears equal to standard FDG-PET imaging for detecting glucose hypometabolism in Alzheimer's disease patients, according to a study published ...
- The Alzheimer’s Death Panelon January 23, 2022 at 1:16 pm
The real reason Medicare won’t pay for a promising treatment.
via Bing News