Phisio Final- Alzheimers

alzs is a neurological disorder in what category

dementia

loss of cognitive abilities

memories, perception issues , motor deficits

Degenerative brain disorder!

alz's causes: Severe degeneration in hippocampus

issue entorhinal cortex (input and output one)

entorhinial cortex

spread to other structures pre-frontal, temporal lobes ( language production), raphe nuclei

The raphe nuclei makes what?

serotonin "dramatic change personality"

identify alzeimers by opening up and finding 2 things

amyloid plaques and neurofibrillary tangles

amyloid plaques are located

extracellular (outside of neuron)

deposit containing a dense core of -amyloid protein

amyloid plaques

specifically: beta-amploid proteins ^

Protein found in excessive amounts in brains of

patients with Alzheimer's disease

Aggregate that forms consists of beta- amyloid protein

( we all have but ) excessive amount in alze. toxic gain of function.

Neurofibrillary tangle

Dying neuron containing intracellular ( neuron from inside) accumulations of twisted protein filaments that formerly served as cell's internal skeleton

Neurofibrillary tangle' s twisted protein

is Tau protein

TAU protein

Protein that normally serves

as a component of microtubules- ( internal fibers= inside of neuron, railroad/ guide)

toxic loss of function

1st genetic of Alzheimer's

The location of slicing by b-secretase.

location of Slicing at b-secretase is controlled by

Presenilian

Presenilian genes on chromosome

1 and 14

Presenlian determines length of

b- amploid protein

APP

precurser for b- AmPloid Protein (A.P.P)

btw every protein has

a precurser, APP cut by presenlian

cut protein twice (gamma/y-secretase cuts the head of) then form the final amyloid fragments:

location of these cuts determines whether a normal-length or longer, more harmful β-amyloid peptide is produced.

# of amino acids is either (2):

40 amino acid protein, or 42 amino acid protein.

42>40 more susceptible to get missfolded and get alzs.

2nd genetic mutation of alzs

ApoE

ApoE

how well u remove missfolded (ubiq process)

2 alleles of ApoE : ( E-4)

interferes with the removal of the long form (42) of ABeta= (amyloid beta peptide.)

Having one allele of ApoE E4 increases the risk of developing Alzheimer's disease.

Having two E4 alleles increases risk even more.

E4 interferes with the brain's ability to clear the long, toxic form of β-amyloid, allowing it to accumulate.

partial loss of function, partial gain?

allele E2 of ApoE

may protect against AD( aka Alzs) development

ApoE chromosome

19

Alzs associated chrosome is

21 - because carries the APP gene (amyloid precursor protein).

environmental factors of alzs include :

obesity, hypertension, high cholesterol, diabetes

traumatic brain injury

level of education

Pharmacological Treatment of alze and other degenerative disorders

acetylcholinesterase inhibitors and an NMDA receptor antagonist•

However, these drugs have no effect on process of

neural degeneration and do not prolong patients' survival

why these treatments ?

Acetylcholinesterase = the "clean-up" enzyme that clears acetylcholine.

Inhibitors stop the clean-up → more ACh → better signaling in AD:

- More acetylcholine stays in the synapse

-Neurons can communicate more effectively

-Memory and cognitive symptoms improve (temporarily)

treatment cont. : NMDA receptor antagonist•

nmda- open calcium channels

Research has also examined the role of calcium dysregulation in Alzheimer's disease. Excessive calcium inside neurons can lead to cell damage and eventually cell death

excessive calcium levels,

Calcium enters the mitochondria

High calcium levels cause calcium to accumulate in the mitochondria—the structures responsible for producing ATP, the cell's energy source.

Calcium binding disrupts mitochondrial function

This essentially halts ATP production.

3. Low ATP = cell cannot survive

begins a path toward cell death

In Alzheimer's disease, excessive calcium enters mitochondria, where it binds to and blocks ATP-producing machinery.

This halts energy production, disrupts the entire cell, and contributes to neuronal death