I can’t remember where I put my things I must be getting AL-ZHEIMER’s DISEASE

I can’t remember where I put my things I must be getting AL-ZHEIMER’s DISEASE

Felwa al-Qazlan

What do former president reagan and actor michael

J. fox have in common?

It Charactarized by memory impairment and other cognitive deficits with preservation of a normal level of consciousness

late features:

Apraxia Short attention span Disorientation language loss (eventually) Depression

Anosognosia*

AL-ZHEIMER’s DISEASE

In AD BOTH short and long term memory are affected

the cases of AD are dividing into 4 main clinical groups :which are

1 -sporadic late onset (most common)2-familial late onset (uncommon)

3 -familial early onset (rare)4 -associated with Down’s syndrome

ETIOLOGY: -It’s the most common age related neurodegenerative

Disease

-4th leading cause of death and the most common cause of Dementia that cause problem with memory among elderly .

- Most cases are sporadic (no known Cause) but 5-10% are familial (rare)!

*The incidence is progressively increased with Advanced age )

familial cases present at 30-40 years old

-Females are affected twice more than males )?( -Down syndrom has been increased the risk of developing AD )?(

Familial forms

EARLY AD : Genetic defect (mutation) in APP (ch 21) or component of gama secretase (presinliin 1(ch14) presinillin 2 (ch1) ,

late AD : apoE4(ch19), SORL1 Ch12 mutation which encodes for alpha-2 macroglobulin

rate of accumlation of AB peptide

Affect the neurons and neuronal function

Small aggregation

1 -neurotransmitter alteration

2 -neurons and synaptic end

toxicity

Large agg. (plaques)

they elicit inflammatory

response leading to

further injury

Neuronal death

Hyperphosphorlation of microtubule

binding protein (tau)

Redisribution of tau from axon to dentrites

and cell body

Aggregation into tangles

Pathogenesis of AD

processing of APP

S APP

Groth factor function

PHYSIOLOGICAL PATHWAY

APP and presenilin mutation

AB40,AB42 formation

AB40 AB42

Aggregation

Amyloid plaques

phosphatase

tau –p ----------- tau ------------<

kinases

Paired helical filaments

Neurofibrillary tangles

NUERONAL DEATH

processing of APP

HOW DOES AD PAITENT BRAIN’S APPEAR GROSSLY?

AND EXPLAIN THE MICROSCOPIC FEATURES OF AD!

Morphology :

GROSSLY : brain is reduced in weight ,cortical atrophy with narrowing of gyri and widening of sulci , white matter loss is accompanied by dilatation of the ventricular system ( compensatory hydrocephalus)

MICROSCOPIC ; the cytopathological hallmarks of AD are:1 -intracellular neurofibrillary tangles (hyperphosphrlated form of TAU protein that

normally binds to microtubules ) _2 -extracellular (senile ) amyloid plaques ( core of beta amyloid peptides surrounding

by altered nerve fibers &reactive glial cells ( in hypocampus ) 3 -amyloid angiopathy

4 -granulovacular degeneration : Multiple, small intraneuronal cytoplasmic vacuoles. Some contain dark granules Known as hirano bodies

There is NO CURE for AD but currently drugs are aimed to either improving the cognition and cholenergic transmission

within CNS or preventing excitotoxic actions resulting from over stimulation of NMDA-glutamate receptors in selected

brail areas .

the pharmacological intervention is only palliative and has short term benefit .

TTT of Alzheimer’s disease

•ACHEIs (donepezil , tacrine , velnacrine ِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِِA- • Rivastigmine , glantamine) 1 -DONEPEZIL ; it has no effect on the course of disease but it can improve

cognitive function

2 -TACRINE ; long acting (6-8hrs)

MOA : all of them are non-competitive inhibitors of ACHE in CNS . Except glantamine ;its competitve

Galantamine may also be acting as an allosteric modulator of the nicotinic receptor in the CNS

Tacrine also inhibit MAO -> decrease release of GABA(inhibitory NT in CNS) +increase norepinephrine, serotonin and dopamine from nerve endings

•NMDA- receptor antagonist ( MEMANTINE) •It neuroprotective and can slow the rate of memory loss , used in moderate and

severe cognitive loss . •It is more effective than ACEIs .

MOA : block NMDA receptor associated ion channel (ca+, Na+)

At theraputic dose : partial blockage of channel . It allows limited ca+ flow throuh unbloked channel to preserve other vital processes that depend on ca .+

What are the NEW TRENDs IN TTT of AD ?

1-vit.E or other antioxidants - protect neuron from free radical damage

(American journal of nursing 2003, KARGER medical and scientific bublisher 2006)-.

-2-ca+ channel blockers. -protect neurons from ca+ ion -induced injury

-(CMAJ canadian medical association 2003)

3-Cholestrol lowering drugs lower brain concentration of Pubmed 2003, medscape ))APOE4

4-Anti-inflammatory drugs for B amyloid aggregate that induce inflammatoty response

(International weekly journal of science 2010)

-5-drugs used in DM as DM has a risk for developing AD later on

NEW YORK ACADEMY OF SCIENCE 2012).

6-Reverse neurodegeneration with new magnesium (compound prohealth 2013 )

Alzheimer’s disease ; it’s the most common cause of dementi

* Etiology ; most of cases are sporadic , few are familial

*Pathogenesis ; deposition of amyloid beta due to genetic defect in precursor

protein

* Gross and microscopic features : hallmark of AD ?

*TTT of AD : no cure for AD but recently drus aimed to eitherimproving the cognition and cholenergic transmission within CNS or preventing excitotoxic actions from over stimulation of NMDA-glutamate receptors

..REFRENCES..

What one memory would you save!

#onememory