Alzheimer’s disease (AD) remains one of the most pressing global health challenges, especially as the aging population continues to grow. This condition steadily erodes memory and thinking skills, severely impacting daily life. New treatments, including monoclonal antibodies such as lecanemab and donanemab, have provided some optimism by slowing cognitive decline. However, these treatments still do not reverse the disease or restore normal brain function.
Recently published reviews Science China Life Science Professor Yan-Jiang Wang and colleagues explore why progress has been limited. Researchers argue that focusing on a single cause is ineffective because Alzheimer’s disease is much more complex. This occurs due to the combined effects of amyloid beta (Aβ) accumulation, tau protein tangles, genetic risk factors, age-related changes, and a wide range of health conditions. Because of this complexity, they suggest that future treatments should take a more comprehensive and tailored approach.
Alzheimer’s disease involves multiple interrelated factors
This review highlights several key areas that are reshaping the way scientists understand Alzheimer’s disease.
Beyond amyloid beta (Aβ)
Amyloid beta has long been a central target in Alzheimer’s disease research, but treatments targeting this protein alone have had limited success. Scientists are now paying close attention to tau hyperphosphorylation, a process that leads to the formation of neurofibrillary tangles and loss of brain cells. Addressing both Aβ and tau may be necessary to more effectively slow disease progression.
Genetic risks and new gene therapies
Genetics plays a big role in determining your risk for Alzheimer’s disease. Although APOE ε4 remains the most widely recognized genetic factor, researchers have identified additional variants associated with specific populations. Advances in genome editing (CRISPR/Cas9) are also being investigated as one-time treatments that could radically alter disease risk.
Aging and general health influence the progression of Alzheimer’s disease
Aging as a central driving force
Aging is the strongest risk factor for Alzheimer’s disease and involves various biological changes. These include decreased mitochondrial function, accumulation of damaged cells, and increased DNA damage. The review points to “senolytic” therapies, which aim to eliminate aging glial cells, as a potential way to improve brain health and slow decline.
Whole body health and the relationship between the gut and brain
Alzheimer’s disease is also affected by symptoms that affect the entire body. Issues such as insulin resistance, high blood pressure, and gut bacterial imbalance can worsen the disease process. Researchers are investigating whether existing diabetes drugs and treatments that target the gut-brain axis can reduce these effects.
Towards integrated and multi-targeted Alzheimer’s disease treatment
The authors emphasize the need to move away from a ‘reductionist’ mindset and towards an ‘integrated strategy’. This change involves the development of treatments that target multiple aspects of the disease at once. It also includes using advanced laboratory models such as human iPS cell-derived organoids to more effectively test new treatments. Additionally, precision medicine approaches based on early biomarkers like plasma pTau217 may allow doctors to identify and treat Alzheimer’s disease earlier and more accurately.
“Defeating Alzheimer’s disease depends on interdisciplinary collaboration and collective innovation,” the authors conclude. Their findings outline a path forward and suggest that with the right combination of strategies, Alzheimer’s disease may eventually become a manageable, even preventable condition, rather than an inevitable decline.
