Alzheimer's disease

What is Alzheimer’s Disease (AD)?

AD is the most common cause of dementia, accounting for about two-thirds of dementia cases in the elderly. It is a neurodegenerative disease that progresses slowly, leading to cognitive decline, depersonalisation, and complete dependence.

What are the two main types of symptoms in Alzheimer’s Disease?

1. Cognitive Deficits: Memory loss, difficulty thinking, problem-solving, and language.

2. Non-cognitive Features (BPSD): Behavioural and psychological symptoms such as depression, agitation, apathy, and psychosis.

What are the key risk factors for Alzheimer’s Disease?

• Age: Risk increases every 5 years after 65.

• Genetic Inheritance: EOAD (early-onset, familial) and LOAD (late-onset, sporadic, linked to APOE ε4).

• Lifestyle & General Health: Cardiovascular health, diet, and exercise.

What are the two main pathological features of Alzheimer’s Disease?

1. Amyloid Plaques: Clumps of β-amyloid protein.

2. Neurofibrillary Tangles: Abnormal aggregates of tau protein.

What is the Amyloid Cascade Hypothesis?

The hypothesis states that the aggregation of β-amyloid (Aβ) triggers a cascade of events leading to synaptic dysfunction, neuroinflammation, and neuronal death, ultimately causing Alzheimer’s Disease.

How does APP processing contribute to Alzheimer’s Disease?

• Alpha-secretase cleavage: Produces neurogenic and neurotrophic proteins (beneficial).

• Beta-secretase cleavage: Produces amyloid-beta monomers, which can clump into toxic oligomers, leading to inflammation and neuronal damage.

What are the current pharmacological treatments for Alzheimer’s Disease?

1. Cholinesterase Inhibitors (e.g., Donepezil): Increase acetylcholine levels to improve cognition.

2. Memantine: NMDA receptor antagonist that regulates glutamate activity to slow cognitive decline.

What is the role of NMDA receptors in Alzheimer’s Disease?

NMDA receptors are glutamate receptors. In AD, excitotoxicity (excessive glutamate activity) contributes to neurodegeneration. Memantine blocks excessive NMDA receptor activity to mitigate this.

What are the novel approaches to treating Alzheimer’s Disease?

1. Secretase Modulators: Reduce Aβ42 production.

2. Anti-Aggregants: Prevent Aβ aggregation.

3. Immunotherapies: Clear Aβ deposits (e.g., monoclonal antibodies like Aducanumab).

Why is early detection critical for Alzheimer’s Disease treatment?

By the time dementia symptoms appear, significant neuronal loss has already occurred. Early detection allows for interventions that can prevent or slow neurodegeneration before irreversible damage.

What are the key biomarkers used in Alzheimer’s Disease?

1. Amyloid Biomarkers: Detect amyloid plaques (e.g., PET imaging, CSF Aβ42).

2. Tau Biomarkers: Detect tau tangles (e.g., CSF tau, tau PET).

3. Neurodegeneration Biomarkers: Measure neuronal injury (e.g., MRI for brain atrophy).