Alzheimer’s disease (AD) is a progressive neurodegenerative condition and the leading cause of dementia. As the global population ages, the need to better understand the disease and develop effective treatments continues to grow. Research has increasingly focused not only on managing symptoms, but also on understanding the biological processes that drive disease progression.

Understanding What Happens in the Brain

Two of the defining features of Alzheimer’s disease are amyloid-beta (Aβ) plaques and neurofibrillary tangles made up of abnormal tau protein.

Amyloid-beta can accumulate outside neurons and form plaques, while abnormal tau can accumulate inside neurons and form tangles. These changes are associated with synaptic dysfunction, neuronal damage, and the progressive cognitive decline seen in Alzheimer’s disease.

These findings have shaped much of Alzheimer’s research, particularly the amyloid hypothesis, which proposes that abnormal amyloid-beta accumulation plays an important role in the development of neurodegeneration. At the same time, growing interest in tau has highlighted that Alzheimer’s is a complex disease involving multiple biological processes.

What May Increase the Risk?

Age remains the most important risk factor for Alzheimer’s disease. However, research has identified several other factors that may influence an individual’s risk.

Vascular conditions such as hypertension, heart disease, and cerebrovascular disease have been associated with cognitive decline and Alzheimer’s. Genetic factors also play a role. The genes APP, PSEN1, and PSEN2 are associated with early-onset familial forms of the disease, while APOE is associated with the more common sporadic form.
Lifestyle and metabolic factors—including physical activity, diet, sleep, smoking, alcohol consumption, and metabolic health—are also being investigated. Some research suggests that healthier lifestyle patterns may be associated with lower dementia risk, although these factors do not guarantee prevention.

How Is Alzheimer’s Currently Treated?

Existing treatments primarily aim to manage symptoms and support cognitive and functional abilities.

Medications such as donepezil, galantamine, and rivastigmine are acetylcholinesterase inhibitors that increase the availability of acetylcholine, a neurotransmitter involved in memory and learning. Memantine, an NMDA receptor antagonist, works through a different mechanism involving glutamate signaling.

Non-pharmacological approaches, including physical activity and cognitive stimulation, may also support physical function, cognitive function, and quality of life. However, evidence for some of these approaches remains inconclusive, highlighting the need for further research.

A Shift Toward Disease-Modifying Therapies

A major development in Alzheimer’s research has been the emergence of therapies designed to target the underlying biology of the disease rather than symptoms alone.

Anti-amyloid antibodies such as lecanemab and donanemab have demonstrated the ability to reduce amyloid burden and slow cognitive decline in clinical trials involving people with early Alzheimer’s disease. The review particularly highlights the phase 3 CLARITY-AD findings for lecanemab.

However, these treatments are not without limitations. Anti-amyloid therapies can cause amyloid-related imaging abnormalities (ARIA), including brain swelling and microhemorrhages, and require ongoing monitoring. Their administration schedules and associated costs can also present practical challenges.

These developments therefore represent progress in Alzheimer’s treatment, but not a cure.

What Comes Next?

The future of Alzheimer’s research extends beyond amyloid.

Researchers are investigating tau-targeting therapies, which aim to interfere with tau aggregation or its spread between neurons. Other approaches include drug repurposing, particularly the investigation of existing medicines that may influence biological pathways involved in Alzheimer’s disease.
Importantly, not every promising treatment has succeeded in clinical development. Several approaches targeting amyloid production have encountered safety or efficacy challenges, illustrating why promising laboratory findings must be rigorously evaluated through clinical trials.

Looking Ahead

Alzheimer’s disease remains a complex condition with no single cause or simple therapeutic solution. Yet research is steadily expanding our understanding of the disease and opening new avenues for treatment.

The development of disease-modifying therapies represents an important step forward, while continued investigation into amyloid, tau, metabolic pathways, and other targets may lead to further advances.

For researchers and the healthcare community, the priority remains clear: developing treatments that can safely delay disease progression and help preserve cognitive and functional abilities for as long as possible.

Reference

Vejandla B, Savani S, Appalaneni R, et al. (January 05, 2024) Alzheimer’s Disease: The Past, Present, and Future of a Globally Progressive Disease. Cureus 16(1): e51705. DOI 10.7759/cureus.51705