Q1 Alzheimers

What is it?

1. Neurodegenerative Disease(or neurological disease)

Characterized by neuron loss in specific areas

Significan neurons loss in the CNS - neurons are dying

A specific type of progressive dementia (there are other dementias)

2. Involving Memory loss and loss of higher cognitve functions

no loss of primary areas

3. Brain autopsies show accumulation of toxic tangles and plaques

Extracellular Plaques (Beta Amyloid Protein)

Intracellular Tangles (Hyperphosphorylated tau protein)

High risk factor is age

45% of People over 85

Early onset <65

late onset >65

Genetic Mutation at differnt Genes but they only account for less than 1% of the occurrence (Importantly shown in patients - swedish) with early onset)

for the rest: cause unknown!

a) Gene that codes for amyloid precursor protein (APP) can have a numver of mutations

b) Mutations involved in the processing of APP (enzymes)so that APP ins inappropriately cleaved

... result of boht a) and b) is a toxic form of of Amyloid called beta amyloid

released in extracellular space forming aggregates called plaques which are toxic

Animal model: An animal model using mice with a mutation in the gene coding for APP can show this

show Impairment

shows age dependet (at 10 month) impairment in learning

Impairments in spatial tasks

show tangles and plaques

can not be positively diagnozed until autopsy

No cure!

Cinical symptoms

Early stage

Loss of Short TermMemory (Can't rememberrecently learned things)

Deficits in attention

Faulty judgement

Decreased initiative(loss of interest in hobbiesor personal hygiene)

Depression

Middle stage

significant Losss of cog. function

significant memoryloss

loss of higher ordre cog func. like inabilty to understand jokes

Emotional problems

agression

irritability

Mood swings

Late stage

loss of cog funct

Memory Loss

Long term memory loss

late stage because ltm is widely distributed

Loss of sense of self:individuals forget who they are

Loss of episodic memoryin Hippocampus

Language break down

Gradual loss of physiological (bodily)functions

Heamorrhage in the brain

because of depostion ofamyloid in blood vessels which makes them rupture

Leading to death

Mean time from diagnosis to death= 7 years

Brain Changes

Loss of neurons

Intracellular: Abnormal changesin Neurons

Plaques

Abnormal extracellular depositsof (normal) Beta-Amyloid Protein surrounded by abnormal neuronal processes and glial cellswho try to get rid of it

Abnormal chnange in extracellular space

NeurofibrilaryTangles

abnormal depositions (filament) in Neurons

Loss of connectivity because of the loss of dentrites and synapses

Loss ofwhole structures

how do the changesaccoutn for clinical symptoms?

Cell Loss leads to loss of structuresor connectiviyin specific areas

Neocortex

Prefrontal cortex

ability to plan andreason is lost

-->hence confusion

loss in highest order assotiation areas

primar areas remain intact(propriocepton; smell, taste touch, vision, hearing)

Lymbic structures

Hippocampus (old cortex) and Entorhinal cortex (neocorte)

learning and memory- short term memoryin particular

are among thefirst areas to degenerate

-->loss of short term memory

Amygdala

the appreciation of theemotional significancof sth. in a normal way is lost

abnormal social behaviour

mood changes

fear

Raphe Nuclei

Regulation of mood(serotonergic projections to the cortex)

depression

Cholinergic Hypothesis(Lack of Neurotransmtters)

Reduced synthesis of the neurotramsmiiteracetylcholine

Amyloid hypothesis(Genetic Problem)

Likely a genetic disease leadingto abnormal/Mutant proteins

However only < 10 percent of the occurrance can be acounted for gene defects

However only 50% of monocygotic twinsdevelope schizophrenia

Likely genetic plus environmental factorsare interacting in some cases

Reminds me of schizophrenia anways ...

factors that increase risk

behaviour factors are under our control (healty life style)

head injury (boxers)

elevated cholesterol and obesity

diabetes

hypertension

arthereosklerosis

smoking

clinical depression

other aren't

Age is highest risk factor

Genes: inheriting a certain allele of a protein apolipo protein e

Difficulty: Other disesaes / dementias show Alzheimer-Like Symptoms

Depression

Stroke

Lesion in the Hippocampus

Schizophrenia

at best: 15% remain undiagnosedbecause they are diagnosed as otherdiseases i.e. depression (impaired memory etc.)

Postive Confirmation: Can only be diagnosedpost-mortem via autopsy

Histological Methods

i.e. microscopy

Currently no diagnosticmethod that can detectAlzheimerswith 100% probabilty

Using a varity of diagnosticmethods

Skilled Doctors

Behavioural assessment

Cognitive Tests

i.e. Memory Tests

Brain Scans(can only be usedto exclude other conditions)

fMRI

MRI

Pet scan

CT

Ethical considerations

Cruel: Its not curable so it's bad news of a slow and certain and cruel death

Subtopic

What if the diagnosis is wrong as in breast cancer

Leading to a self fulfilling prophecy?

Would insurances make you test

Would employers make you test

Other drawbacks

Does not have to break out

As shows Schizophrenia evenif identical twin has it there is onlya 50% chance

So there is an environmentalside to it

Still only 90% probabilty