Alzheimer's and Stroke

What is the highest risk factor for AD?

Age.

What protein is amyloid-β derived from?

Amyloid Precursor Protein (APP).

Where is the APP gene located?

Chromosome 21.

Why do people with Down’s syndrome (trisomy 21) often develop AD?

They have an extra copy of the APP gene, leading to increased amyloid-β production.

What enzymes cleave APP to produce amyloid-β?

β-secretase and γ-secretase.

What are the two types of amyloid-β produced by β-secretase cleavage?

Aβ1-40 and Aβ1-42.

What happens if APP is cleaved by alpha and gamma secretase?

It produces a protein beneficial for learning and memory, not amyloid-β

What is the normal function of Tau protein?

• Tau stabilizes microtubules, which are essential for intracellular transport.

What happens to Tau in AD?

It becomes hyperphosphorylated, leading to the formation of neurofibrillary tangles and disruption of cellular transport.

What are the genetic mutations associated with early-onset AD?

Mutations in APP, Presenilin 1, and Presenilin 2 genes.

What is the role of ApoE in late-onset AD?

ApoE transports cholesterol and binds amyloid-β. The ApoE*4 allele is a risk factor for AD.

How is amyloid-β transported out of endothelial cells?

Through efflux transporters like P-gp, MRP5, and BCRP.

What are the two main types of stroke?

Ischemic stroke (80%) and hemorrhagic stroke.

What causes an ischemic stroke?

Disruption of blood supply due to a clot or plaque (atherosclerosis).

What causes a hemorrhagic stroke?

Bleeding into the brain.

What are the two regions of damage in ischemic stroke?

Umbra (irrecoverable damage) and penumbra (potential recovery).

What is the key inflammatory cytokine in stroke?

Interleukin-1β (IL-1β).

how does Interleukin-1β exacerbate brain damage

Interleukin 1 beta binds to interleukin 1 receptor 1

Transcription factor (NFkB) binds to DNA to produced interleukin 6 and TNF leading to more inflammation and cell death

What is the primary treatment for ischemic stroke within 4.5 hours?

Tissue Plasminogen Activator (Alteplase).

What are the surgical options for hemorrhagic stroke?

Craniotomy to repair blood vessels or remove clots.