Untitled Flashcard Set

ALZHEIMERS DISEASE

🧠 ALZHEIMER’S DISEASE — COMPLETE NOTES

🧩 1. What is Alzheimer’s Disease?

  • Most common cause of dementia (>50%)

  • Progressive, irreversible brain disorder

  • Named after Alois Alzheimer

🔹 Key Features:

  • Memory loss

  • Confusion

  • Personality changes

  • Cognitive decline

📊 2. Key Facts

  • Usually starts after age 65

  • ~50% of people >85 affected

  • Incurable

  • Major cause of nursing home admissions

⚠ 3. AETIOLOGY (CAUSES / RISK FACTORS)

Alzheimer’s is MULTIFACTORIAL → many factors contribute

🧓 A. Age (MOST IMPORTANT)

  • Risk ↑ dramatically with age

  • Brain changes with ageing:

    • ↓ brain size

    • ↓ synapses

    • ↑ amyloid deposits

🧬 B. Genetics (VERY IMPORTANT)

👉 ~70% of cases linked to genetics

Key Genes:

  1. Amyloid precursor protein (APP)

    • Located on chromosome 21

    • Mutations → ↑ beta-amyloid

  2. Presenilin 1 & 2

    • Involved in amyloid production

  3. Apolipoprotein E (ApoE)

    • Important for cholesterol + myelin

  4. Oestrogen receptor

    • Explains higher risk in postmenopausal women

👶 Early-Onset Alzheimer’s

  • Age: 30–60 years

  • Rare (1–6%)

  • Inherited (autosomal dominant)

🌍 C. Environmental Factors

Air pollution

  • Causes:

    • Oxidative stress

    • Inflammation

    • ↑ amyloid deposition

Diet

  • Protective:

    • Antioxidants

    • Vitamins

  • Harmful:

    • High saturated fat

    • Processed foods

Malnutrition

  • Low:

    • Vitamin B12

    • Folate

    • Vitamin D

Metals

  • Possible role:

    • Aluminium

    • Lead

    • Iron imbalance

🦠 D. Infections

Viruses:

  • HSV-1, HSV-2

  • HIV

  • Hepatitis C

  • CMV

  • HPV

  • Varicella-zoster

Non-viral:

  • Syphilis

  • Chlamydia

  • Helicobacter pylori

  • Periodontal disease

  • Lyme disease

👉 Multiple infections = higher risk (synergistic effect)

💉 Interesting:

Vaccinations (e.g. flu, herpes zoster) may reduce risk

❤ E. Medical Conditions

  • Head injury

  • Stroke

  • Hypertension

  • Atrial fibrillation

  • Obesity

  • Diabetes mellitus

🦠 F. Gut-Brain Axis

  • Alzheimer’s linked to gut microbiome imbalance

  • Possible effects:

    • Blood-brain barrier dysfunction

    • Immune changes

    • Neuroinflammation

🔬 4. PATHOGENESIS (WHAT’S HAPPENING IN THE BRAIN)

This is the MOST IMPORTANT EXAM SECTION

🧠 Main Brain Changes:

  1. Cortical atrophy

  2. Beta-amyloid plaques

  3. Neurofibrillary tangles (tau)

  4. Loss of cholinergic neurons

  5. Neuroinflammation

1⃣ Cortical Atrophy

What happens:

  • Brain shrinks

  • Especially:

    • Frontal lobe

    • Parietal lobe

Effects:

  • Memory loss

  • Behaviour changes

2⃣ Beta-Amyloid Plaques (CORE MECHANISM)

Step-by-step:

  1. APP protein is broken down

  2. If cut by wrong enzymes (beta + gamma secretase):
    → forms beta-amyloid

  3. Beta-amyloid:

    • Sticky

    • Clumps together → plaques

Effects of plaques:

  • Trigger inflammation

  • Damage synapses

  • Impair communication between neurons

  • Cause memory loss

3⃣ Neurofibrillary Tangles (Tau Protein)

Normal:

  • Tau stabilises microtubules in neurons

In Alzheimer’s:

  • Tau becomes hyperphosphorylated

  • Loses function

  • Clumps → tangles

Effects:

  • Disrupts neuron structure

  • Blocks transport inside cells

  • Causes cell death

4⃣ Cholinergic Neuron Degeneration

  • ↓ Acetylcholine (ACh)

Why important:

ACh is needed for:

  • Memory

  • Learning

  • Attention

Clinical link:

  • Drugs = acetylcholinesterase inhibitors
    → increase ACh levels

5⃣ Neuroinflammation

  • Caused by amyloid plaques

  • Leads to:

    • Neuron damage

    • Disease progression

🧠 5. CLINICAL MANIFESTATIONS (SYMPTOMS)

🟢 Early (Preclinical / Mild)

  • Mild memory loss

  • Poor concentration

  • Disorientation

🟡 Moderate

  • Difficulty recognising family

  • Trouble reading/writing

  • Increased confusion

🔴 Severe (Late)

  • Bedridden

  • Loss of speech

  • Cannot swallow

  • Fully dependent

🧠 💡 BIG PICTURE SUMMARY (FOR EXAMS)

🧾 Aetiology:

  • Age (MOST IMPORTANT)

  • Genetics (APP, presenilin, ApoE)

  • Environment (diet, pollution)

  • Infections

  • Medical conditions

🔬 Pathogenesis:

  • Beta-amyloid plaques → synapse damage

  • Tau tangles → neuron death

  • ↓ Acetylcholine → memory loss

  • Brain atrophy

  • Neuroinflammation

⚠ Clinical Manifestations:

  • Memory loss → confusion → personality change → total dependence