Waste-disposal protein key to AMD and Alzheimer’s, study says

New research identifies a cellular waste-sensing protein may be behind age-related macular degeneration, as well as Alzheimer’s


A treatment targeting problem proteins in Alzheimer’s disease could also cure age-related macular degeneration (AMD), scientists behind a new study suggest.

The research, published this week in the journal PLOS ONE, found what was happening at the cellular level in the brain of Alzheimer’s patients was also occurring in the eyes of people with AMD.

Scientists have long sought the answer to why ‘junk’ proteins, including amyloid-beta, build up in the brains of Alzheimer’s patients, interfering with normal cognitive function.

The protein TREM2 – which stands for “triggering receptor expressed in microglia” – is thought to be involved. In healthy brains, it senses waste and activates the ‘housekeeper’ cell it is part of. But the levels of TREM2 protein are insufficient in the brain of an Alzheimer’s patient.

The research, led by Louisiana State University professor, Dr Walter Lukiw, found a similar pattern of lowered TREM2 in the retina of dry AMD patients.

As the small, sticky and toxic proteins are not properly cleaned by the microglial ‘housekeepers’, they may accumulate in the eye as drusen, Dr Lukiw explained.

The team also found that high levels of a small fragment of RNA – known as microRNA-34a – was partly responsible for the lowered amounts of TREM2.

Dr Lukiw concluded: “[This] indicates that getting rid of the excessive miRNA-34a to restore normal TREM2 abundance may provide a highly effective therapeutic strategy for the treatment of both degenerative diseases of the brain, such as Alzheimer’s disease, and progressive diseases of the retina, such as AMD.”

University of Manchester clinical ophthalmologist, Dr Tiarnan Keenan, who was not involved in the study, said the research provided some “interesting and exciting” information.

But he told OT that scientists were not as sure of the causative link between amyloid-beta and AMD as they were for the protein and Alzheimer’s. The amyloid-beta in drusen may simply be a by-product, Dr Keenan noted.

He explained: “It is tempting from this work to think that TREM2 deficits and amyloid-beta accumulation may have causative roles in AMD formation, as they seem to in Alzheimer’s disease.

“However, it is noticeable that associations have been found between genetic variants in TREM2 and Alzheimer’s disease, but not between these variants and AMD. Of course, future genetic studies in this area may demonstrate a link, and would now be very timely.”

Dr Keenan said that his own research, tracking 65,000 people with AMD and 168,000 people with dementia over 12 years, showed there was no link between patients developing the diseases.

He added: “While Alzheimer’s disease and AMD share environmental risk factors and pathological features, their coexistence at the individual level is no different from that expected by chance.”

He theorised that it was possible that amyloid-beta build-up might be one factor in many causing AMD, which he said is predominantly a genetic disease.

“In this context, targeting amyloid-beta accumulation might conceivably reduce AMD progression, but this is far from certain,” he concluded.