Scientists discover earliest yet sign of Alzheimer’s raising new hopes of preventing disease

SCIENTISTS have discovered the earliest yet sign of Alzheimer’s in the brain, heralding new ways of spotting and preventing the disease.

A surge of a specific protein in the brain called PSD-95 is a key hallmark of the beginnings of Alzheimer’s disease and the earliest one identified so far, US researchers said.

Studying the brains of mice, the team from the University of Illinois Urbana-Champaign also found that this increased protein activity also leads to the seizures associated with the earliest stages of neurodegeneration.

This is the progressive loss of neurons in the brain associated with diseases like Alzheimer’s.

Scientists found that inhibiting PSD-95 in mice meant mice experienced fewer seizures.

Study leader Nien-Pei Tsai, an Illinois professor of molecular and integrative physiology, said research into the protein could help find new way to diagnose Alzheimer’s early and treat it.

Dr Tsai’s team usually studies mice that make more amyloid-beta proteins, which fuel the formation plaques in the brain in people with Alzheimer’s and hamper neural activity.

These proteins are a key hallmark of the disease and have been the subject of lots of research.

But the researchers decided to focus on a much earlier time frame that hasn’t been studied before, when no other markers or abnormalities have been reported.

Dr Tsai said: “We were thinking, if we can catch anything that is happening early enough, maybe we can find a way to diagnose the disease earlier or slow down the progression.

“We know that Alzheimer’s is irreversible. But if we can slow down the progression or even delay the onset of the disease, we can improve the quality of life for patients.”

Studying neuron cultures and then in live mice, researchers noticed higher levels of PSD-95.

“Our data suggests that the elevated PSD-95 is contributing to hyperexcitability in the brain,” Dr Tsai explained.

“That’s a common phenotype is some of the early stages of Alzheimer’s disease patients.

“They tend to have hyperexcitability or elevated seizure susceptibility in the brain, preceding and exacerbating the neurodegeneration that follows.”

To confirm that increased PSD-95 was causing seizures, the researchers inhibited PSD-95 in some of the mice.

These mice experienced fewer seizures and were less likely to die from them too.

“Our findings show that PSD-95 is a critical contributor to the hyperexcitability in the earliest stages of Alzheimer’s,” Dr Tsai said.

“So we think that PSD-95 can be an early biomarker to indicate that a patient could have Alzheimer’s disease or elevated seizure susceptibility.”

The findings – published in the journal EMBO reports – could also herald future treatment options too.

“In terms of treatment, antibody inhibitors for PSD-95 could be useful in the early onset of Alzheimer’s, with more clinical study,” Dr Tsai said.

The team now hope to test whether their discovery also applies to human Alzheimer’s patients too.

Researchers from University College London identified a new early warning sign of Alzheimer’s that may show in people as young as 40 – and 25 years before symptoms.