Alzheimers disease research

Last century, my grandfather came down with what was just termed dementia or senile dementia, and was eventually confined to what was called a mental institution, where he eventually died. I knew there had been a problem for a while, because my father would occasionally get a panicked call from his mother to drive out to their suburb to go and search for his father. He usually knew where to look, because of what his father had taken with him, which included some rope and sundry other items which you needed to catch brumbies. My father and grandfather used to go catching brumbies during the 1930s, and my father would break them in. I think they sold some but kept a couple over the years. Many years later, my father was diagnosed with Alzheimers Disease, but died from kidney failure long before it robbed him of more than a few of his memories. So, as I am sure you can imagine, keeping tabs on Alzheimers Disease research is something that is important to me.

On November 3, 1906, a clinical psychiatrist and neuroanatomist, Alois Alzheimer, reported “A peculiar severe disease process of the cerebral cortex” to the 37th Meeting of South-West German Psychiatrists in Tübingen, He described a 50-year-old woman whom he had followed from her admission for paranoia, progressive sleep and memory disturbance, aggression, and confusion, until her death 5 years later. His report noted distinctive plaques and neurofibrillary tangles in the brain histology. It excited little interest despite an enthusiastic response from Emil Kraepelin, who promptly included “Alzheimer’s Disease” in the 8th edition of his text Psychiatrie in 1910. Alzheimer published three further cases in 1909 and a “plaque-only” variant in 1911, which reexamination of the original specimens in 1993 showed to be a different stage of the same process, Alzheimer died in 1915, aged 51, soon after gaining the chair of psychiatry in Breslau, and long before his name became a household word¹.

Alzheimer’s disease leaves three main physical traces in the brain: amyloid plaques, tau tangles and widespread brain cell death. Together, these changes destroy brain tissue and cause permanent cognitive loss².

The plaques are abnormal clumps of beta-amyloid protein that form in the spaces between neurons. They block electrical and chemical signals between neurons. The tangles are twisted abnormal strands of a protein called tau that form inside neurons. Normal tau proteins act like conduits that carry nutrients through the cell, but when these are tangled, they interrupt this flow and starve the cell of the nutrients the cell needs. As the plaques and tangles spread, neurons die, and the brain starts to shrink. This process usually starts in the hippocampus, the part of the brain responsible for learning and making new memories. The shrinkage slowly spreads to the parts of the brain that control language, reasoning and social behaviour. In late stages, the brain is significantly smaller than a healthy brain. To make matters worse, the brain’s immune cells attempt to clean up the toxic plaques and tangles, leading to chronic inflammation, reducing blood flow and preventing the brain from getting enough oxygen and glucose, further impairing brain function².

These plaques and tangles often start developing 10 to 20 years before any symptoms appear. However they can be detected by imaging using PET scans, MRI scans or by blood tests; the latter are used to measure abnormal proteins in the body².

Alzheimer’s Disease research seems to have reached a major turning point, shifting from only managing symptoms to fundamentally altering the disease’s biology. The most recent breakthroughs include advanced drug therapies, new diagnostic tools, and new ways of preventing cognitive decline³.

The new drug therapies include monoclonal antibodies which clear the beta-amyloid plaques. These have been shown in clinical trials to slow early stage cognitive decline by 30%. Over 150 other drugs are currently undergoing clinical trials. Some of these target the amyloid plaques, the tau tangles, and the chronic inflammation among others³.

There are also breakthroughs in early detection and diagnosis. There are now high accuracy blood tests which detect specific forms of tau and amyloid proteins, long before clinical symptoms emerge. Another technique is using EEG to detect subtle changes in brainwaves linked to early mild cognitive impairment. There are also improved MRI scanning techniques³.

Where things are really changing is in the approach at the systemic biological level. Researchers have identified that chronic inflammation and malfunctioning microglia (the brain’s immune cells) drive cellular death. Safely blocking an immune molecule called STING has been shown to halt plaque formation and prevent memory loss in preclinical models. Another target is the IDOL enzyme, which, when blocked, sharply reduces plaque build-up. Concurrently, novel copper-based compounds have demonstrated an ability to recharge the brain’s natural clearance systems. There are also studies looking at “bioenergetic failure” that have found restoring the energy balance in malfunctioning mitochondria can reverse advanced cognitive decline in lab models, offering a new therapeutic angle³.

Then there was the effect of the shingles vaccine which, to me, came like a bolt out of the blue after I had just had my second injection⁴. Massive long term population studies have uncovered a link between routine vaccinations—specifically the shingles vaccine—and a 20% reduction in long-term dementia risk, reinforcing the role of general immune system health³.

The global number of persons with Alzheimers Disease dementia, mild Alzheimers Disease cognitive impairment, and preclinical Alzheimers Disease, have been estimated at 32, 69 and 315 million, respectively. Together they constituted 416 million across the Alzheimers Disease continuum, or 22% of all persons aged 50 and above⁵.

In Australia, there are about 480,000 people living with dementia, 70% (i.e. ~336,000) of whom have Alzheimers Disease. Around 175 Australians are diagnosed with Alzheimers Disease every day. That number will increase as our population ages. It has been estimated that about 4.5 million Australians will be diagnosed with Alzheimers Disease in the next 40 years⁶. That is a burden on all of us, and it can be prevented only by more research.

Sources

1. https://pubmed.ncbi.nlm.nih.gov/22034141/
2. https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/what-happens-brain-alzheimers-disease
3. https://www.weforum.org/stories/2026/04/alzheimers-disease-breakthroughs-health/
4. https://blotreport.com/2023/12/05/the-shingle-vaccines-other-benefits/
5. https://pubmed.ncbi.nlm.nih.gov/35652476/
6. https://alzheimersresearch.org.au/alzheimers/impact/