Alzheimer's disease

Alzheimer’s disease is the most common cause of dementia. It is a progressive neurological condition that gradually damages brain cells, leading to difficulties with memory, thinking, behaviour and everyday functioning. The disease is named after the German psychiatrist Alois Alzheimer, who first described the condition in 1906.

Although Alzheimer’s disease most commonly affects older adults, it can also occur in younger people. In rare cases, symptoms can appear as early as a person’s 30s. Women are diagnosed slightly more often than men, although researchers are still investigating the reasons for this difference.

What happens in the brain?

Alzheimer’s disease causes progressive loss of brain tissue and is associated with the build-up of two abnormal proteins in the brain:

Amyloid-beta
Tau

These proteins accumulate and form structures known as amyloid plaques and tau tangles, which disrupt communication between brain cells and eventually lead to neuron death.

Over time, this damage affects areas of the brain responsible for memory, reasoning, personality and behaviour.

Common symptoms of Alzheimer’s disease

Early symptoms of Alzheimer’s disease often involve changes in memory and thinking. These may include:

Difficulty remembering recent events or conversations
Problems with reasoning or decision-making
Changes in personality or behaviour
Confusion about time or place
Difficulty performing familiar daily tasks

As the disease progresses, people may need increasing levels of support with everyday activities. Memory problems are the most widely recognised symptom and are often the reason people first seek medical advice.

Variants of Alzheimer’s disease

Not all people with Alzheimer’s disease experience memory loss first. Some forms of the disease affect other areas of the brain, leading to different early symptoms.

Posterior Cortical Atrophy (PCA)

Posterior Cortical Atrophy (PCA), sometimes called Benson’s syndrome, affects areas of the brain responsible for visual processing and spatial awareness.

People with PCA may experience:

Difficulty interpreting visual information
Problems judging distances or navigating spaces
Challenges with reading, spelling or calculations

Because these symptoms involve vision, many people initially visit an optometrist, believing they have an eye problem.

PCA often affects people at a younger age, typically in their 50s, and can be difficult to diagnose early because memory may remain relatively intact.

Primary Progressive Aphasia (PPA)

Primary Progressive Aphasia (PPA) primarily affects the brain regions responsible for language. Early symptoms often include:

Difficulty finding the right words in conversation
Mispronouncing words
Problems understanding or forming sentences

Language difficulties gradually worsen over time as the disease progresses.

Causes and risk factors

For most people, the exact cause of Alzheimer’s disease is unknown. These cases are known as sporadic Alzheimer’s disease. Researchers believe the condition develops due to a complex interaction of:

Genetic factors
Lifestyle factors
Environmental influences

Scientists have identified more than 70 genetic risk factors associated with Alzheimer’s disease, although many of their effects are still being studied.

The ApoE gene and Alzheimer’s risk

One of the most important genetic risk factors for Alzheimer’s disease is the Apolipoprotein E (ApoE) gene.

The ApoE gene exists in three common forms:

Each person inherits one copy of the gene from each biological parent.

For example:

ApoE2/E3 means one E2 allele and one E3 allele.

People who inherit the ApoE4 variant have an increased risk of developing Alzheimer’s disease. Individuals who inherit two copies (ApoE4/E4) have an even higher risk.

However, ApoE status does not determine whether someone will develop Alzheimer’s disease.

Many people with ApoE4 never develop the disease.
Some people without ApoE4 still develop Alzheimer’s.

Because of this, ApoE testing is not commonly used as a clinical diagnostic tool.

Rare inherited forms of Alzheimer’s disease

A small percentage of Alzheimer’s cases are caused by inherited genetic mutations.These mutations follow an autosomal dominant inheritance pattern, meaning that a person only needs to inherit one copy of the faulty gene from a parent to develop the disease. If a parent carries one of these mutations, each child has a 50% chance of inheriting it. These inherited forms of Alzheimer’s disease typically appear at a younger age, sometimes in a person’s 30s or 40s.

Three genes are known to cause inherited Alzheimer’s disease when mutated:

APP (Amyloid Precursor Protein)
PSEN1 (Presenilin 1)
PSEN2 (Presenilin 2)

Mutations in these genes lead to increased production of amyloid-beta, resulting in plaque formation and progressive neuron loss.

The biology of Alzheimer’s disease

Amyloid-beta

Amyloid-beta is a protein produced naturally by neurons in the brain, particularly in areas involved in memory, such as the hippocampus and the neocortex. Although its full function is not completely understood, amyloid-beta is believed to play roles in:

Memory processes
Communication between neurons
Neurogenesis (the creation of new brain cells)

Problems arise when amyloid-beta production exceeds the brain’s ability to remove it. When this happens, the protein begins to accumulate around neurons, forming amyloid plaques. These plaques can:

Disrupt communication between neurons
Reduce synaptic signalling
Contribute to the eventual death of brain cells

Some scientists believe amyloid-beta accumulation may also trigger changes in another protein involved in Alzheimer’s disease: tau. Recent drug trials have successfully removed amyloid plaques from the brain, but in many cases cognitive decline continued. This suggests that amyloid alone may not fully explain the disease and that other processes, including tau pathology, are also important.

Tau protein

Tau is a protein that helps maintain the internal structure of neurons, particularly within axons, the long fibres that transmit signals between brain cells. In Alzheimer’s disease, abnormal chemical changes cause tau proteins to detach and accumulate inside neurons. These proteins form twisted structures known as neurofibrillary tangles.

Tau tangles disrupt several critical cellular processes, including:

Mitochondrial function
Protein recycling and degradation
Synaptic plasticity (the brain’s ability to adapt and form new connections)

As these processes fail, neurons gradually lose function and die. Researchers are continuing to study how amyloid-beta and tau interact, and how these proteins may influence each other in the development and progression of Alzheimer’s disease.