Amyloid Fragments Found In Young Brains

Researchers at Northwestern University have uncovered evidence that the development of AD may begin in people as young as age 20.

Alaina Baker-Nigh, Ph.D.

This new study, published in the journal Brain, is significant for visualizing for the first time a hallmark of AD—sticky clumps of beta amyloid—at such an early age. Beta amyloid fragments are produced from the regulated cleavage of a brain protein called APP; over time they converge and grow, becoming more toxic along the way.

“These findings are not a call for alarm, however,” said Alaina Baker-Nigh, Ph.D., a postdoctoral fellow at Washington University School of Medicine. “The presence of amyloid is not a marker indicating disease, but it may help us identify the point at which a normal brain flips the switch and becomes pathological.”

Baker-Nigh added that the amyloid clumps were contained within one specific type of neuron known as the basal forebrain cholinergic neuron (BFCN). These neurons are involved in memory and attention and are the most vulnerable to damage from AD; by the late stages of AD, almost all BFCNs are typically destroyed.

Baker-Nigh and her colleagues examined these neurons from the brains of three groups of deceased individuals: 13 cognitively normal young people (ages 20 to 66); 16 nondemented older people (ages 70 to 99); and 21 people with AD (ages 60 to 95). The 16 older people without dementia included two “super-aged” ones who were 90 and 95 but performed as well as someone decades younger on memory tests.

The researchers identified beta amyloid fragments in every brain sample they looked at, and the total amount was roughly the same regardless of age. However, as people got older, the amyloid was present in larger particles, suggesting these protein fragments exist naturally in the neuron—and possibly serve some purpose—but gradually clump over time.

Interestingly, the largest clumps were found in the oldest healthy adults, as opposed to those with AD. The reason for this phenomenon is not clear, but Baker-Nigh believes it may reflect that the BFCNs in the AD people were already dead, and thus the amyloids stopped growing.

“Therefore, the key factor for determining brain health may not be how big the amyloid clumps get but how well your cells tolerate the clumping,” she told Psychiatric News.

The next step in research would involve pinpointing exactly how these amyloid clumps kill a BFCN, which might help identify the best way to protect these vulnerable cells, which in turn may help protect the rest of the brain. A clue might be found in “super-aged” seniors, as the two brain samples in this analysis actually displayed some of the lowest levels of amyloid clumping.

Another area to pursue would be how this beta amyloid accumulation connects with a protein called Tau, which is also believed to be a key contributor in the progression of AD.

“Because Alzheimer’s usually manifests in later life, we don’t necessarily have to prevent these amyloids from forming,” Baker-Nigh said. “If we can find a good time for early intervention that could delay the process even for only a few years, it would still reduce the burden of Alzheimer’s tremendously.”

This work was supported by grants from the National Institute on Aging as well as a Zenith Fellows Award from the Alzheimer’s Association. ■