Neurodegenerative disorders Flashcards
describe the main characteristics of neurodegenerative disorders
- progressibe and irreversible LOSS OF NEURONS
- etiology involved injury of specific type of neuronal cell and their location
- due to both GENETIC and ENVIRONMENTAL FACTORS
- patholgy includes cellular AGGREGATION OF MISFOLDED PROTEINS
Alzeimers disease General background
- loss of hippocampal and cortical neurons results in impaired membory formation and cognitive deficits
- extracellular Beta-amyloid plaques and intracytoplasmic neurofibrillary tangles
Parkinsons and huntington’s
- loss of dopaminergic neurons in basal ganglia leads to altered movement control
- Parkinsons = alpha-synuclein
= Huntingtons = intranuclear inclusions of huntingtin protein
Cognitive sympoms of Alzheimer’s disease (AD)
- Loss of short-term memory = poor recall and losing items
- Aphasia = diffuclty remembering words to being completely unable to speak, read or write
- Apraxia = inability to carry out motor activities despite intact motor system
- Agnosia = inability to recognize objects, person, sounds, shapes, or smells despite intact sensory sytstems
- Disorientation = impaired perception of time
Non-cognitive sysmptoms of Alzheimer’s disease
- DEPRESSION
- pSYCHOTIC SYMPTOMS
- behavior disturbances (agression, motor hyperactivity, repetitive mannerisms)
describe the pathology of alzeimer’s disease
Massive tissue damage and decreased brain volume
- Neuronal degeneration and cortical atrophy
- Neuritic plaques (amyloid or senile plaques)
- Neurofibrillary tangles
** these cahnges eventually lead to clinical symptoms, but they begin years before onset of symptoms
**Brain Atrphy**
What regions of the brain are affected by alzheimer’s disease
- Parietal lobe
- frontal lobe
- temporal lobe
- hippocampus
- nucleus of meynert
Describe cholinergic hypothesis for the pathogenesis of alzhiemers
- DEFICIENCY OF ACETYLCHOLINE
–> due to degeneration of subcortical cholinergic neurons in the **memory formation areas (hippocampus)**
–> Atropine can induce confusional states, similar to dementia of AD
–> loss of ACh activity correlates with severity of AD
–> AChE inhibitors –> do not prevent dementia, but slow progression of AD
describe amyloid hypothesis in alzheimers pathogenesis
- EXTRACELLULAR ACCUMULATIONS OF BETA-AMYLOID PEPTIDES (BetaA) that are toxic to neurons
–> Beta-amyloid is cleaved from amyloid precursor proteins (APP) located on cell membrane
–> imbalances between the production and clearance of Beta-amyloid
–> APP gene is on chromosome 21, people with trisomy 21 have extra copies of APP and commonly exhibit AD by age of 40
- DEPOSITION OF BETA-AMYLOID PLAQUES DOES NOT CORRELATE WITH NEURONAL LOSS
describe the two types of AD
- EArly onset
–> related to mutations in APP gene that encodes amyloid-Beta precursor peptides
–> result is OVERPRODUCTION OF beta-amyloid
–> related to mutations PSEN1 and PSEN2 genes which involved in membrane proteins that cleave APP
- LATE onset AD (common)
–> ε4 allele of APOE (encodes apolipoprotein E)
–> ApoE enhances proteolytic breadkwon and clearance of ABeta within and between cells
–> 3-fold higher risk of developing AD
descrive Tau hypothesis of alzheimers pathogenesis
- Microtubule-associated protein Tau
–> tau provides support to microtubules and neuronal cytoskeleton
–> HYPERPHOSPHORYLATION OF TAU –> aggregates and forms NEUROFIBRILLAY TANGLES
- CAUSES:
–> microtubular disintergration and instability
–> collapse of neuronal transport system
–> altered NT release and synaptic function
–> CELL DEATH
Describe the tx of non-cognitive symtpoms of AD
PSYCHOSIS/AGITATED BEHAVIOR
- Atypical antipsychotics (risperidone, olanzapine and quetiapine)
–> Adverse = parkinsonism, sedation, higher risk of stroke and falls in elderly patients
- Cholinesterase inhibitors
Describe the tx of non-cognitive symtpoms in AD
DEPRESSION AND ANXIETY
- SSRI
–> better side effect profile in elderly
–> SERTRALINE or CITALOPRAM
- AVOID TRICYCLICS (TCAs)
–> Avoid due to seadation, confusition, ANTICHOLINERGIC EFFECTS
–> ORTHOSTATIC HYPOTENSION = BAD FOR ELDERLY
