New compound shows promise in treatment of Alzheimer’s

Some researchers have identified a drinkable cocktail of designer molecules that interferes with a crucial first step of Alzheimer’s and even restores memories in mice.

The binding of amyloid beta peptides to prion proteins triggers a cascade of devasting events in the progression of Alzheimer’s — accumulation of plaques, a destructive immune system response, and damage to synapses.

“We wanted to find molecules that might have a therapeutic effect on this network,” said senior author.

Researchers screened tens of thousands of compounds looking for molecules that might interfere with the damaging prion protein interaction with amyloid beta. They found that an old antibiotic looked like a promising candidate but was only active after decomposing to form a polymer. Related small polymers retained the benefit and also managed to pass through the blood-brain barrier.

They then dissolved the optimized polymeric compound and fed it to mice engineered to have a condition that mimics Alzheimer’s. They found that synapses in the brains were repaired and mice recovered lost memory.

A collaborating team  reported a positive response when they delivered the same cocktail to cells modeled to have Creutzfeldt-Jakob Disease, a devasting neurological condition caused by infection with misfolded prion protein.

The next step is to verify the compounds aren’t toxic in preparation for translation to clinical trials for Alzheimer’s disease.

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New blood test to diagnose Alzheimer's early

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 A new blood test may potentially help detect Alzheimer's disease at an early stage, giving people up to 15 years warning before the symptoms appear, scientists say.

The test is based on an immuno-chemical analysis using an infrared sensor. The sensor's surface is coated with highly specific antibodies which extract biomarkers for Alzheimer's from the blood or the cerebrospinal fluid, taken from the lower part of the back (lumbar liquor), researchers said.

The infrared sensor analyses if the biomarkers show already pathological changes, which can take place more than 15 years before any clinical symptoms appear, they said.

A major problem of Alzheimer's disease diagnosis is the fact that, by the time the first clinical symptoms appear, massive irreversible damage to the brain has already occurred. At that point, symptomatic treatment is the only available option, researchers said.

"If we wish to have a drug at our disposal that can significantly inhibit the progress of the disease, we need blood tests that detect Alzheimer's in its pre-dementia stages," said Klaus Gerwert from Ruhr-University Bochum in Germany.

For the novel test, the secondary structure of the so-called Amyloid beta peptides serves as biomarker. This structure changes in Alzheimer's patients, researchers said.

In the misfolded, pathological structure, more and more Amyloid beta peptides can accumulate, gradually forming visible plaque deposits in the brain that are typical for Alzheimer's disease. This happens more than 15 years before first clinical symptoms appear, they said.

The pathological beta Amyloid plaques can be temporarily detected by positron emission tomography (Amyloid PET) but this procedure is comparatively expensive and is accompanied by radiation exposure, they said.

Together with researchers from German Centre for Neurogenerative Diseases (DZNE), Gerwert and colleagues developed an infrared sensor for detecting misfolding of Amyloid beta peptides.

The infrared sensor extracts the Amyloid beta peptide from body fluids. After initially working with cerebrospinal fluid, the researchers subsequently expanded the method towards blood analysis.

"We do not merely select one single possible folding arrangement of the peptide; rather, we detect how all existing Amyloid beta secondary structures are distributed, in their healthy and in their pathological forms," said Gerwert.

Researchers analysed samples from 141 patients. They achieved a diagnostic precision of 84 per cent in the blood and 90 per cent in cerebrospinal fluid, compared with the clinical gold standard.

The test showed an increase of misfolded biomarkers as spectral shift of Amyloid beta band below threshold, thus diagnosing Alzheimer's, researchers said.

The findings were published in the journal Biophotonics.