Alzheimer's disease Flashcards
Alzheimer’s Disease
Degeneration of cortical and cholinergic neurons in basal nucleus of Meynert
● 60%~90% loss of choline acetyltransferase in cerebral cortex
● senile plaques (beta amyloid deposited in gray matter of the brain)
nucleus basalis of Meynert (NBM)
define:
nucleus basalis of Meynert (NBM)T
is a large source of cholinergic innervation to widespread cortical areas.
This is an area that degenerates in AD and other neurodegenerative illnesses
AD
Symptoms:
● progressive dementia.
● Patients become increasingly forgetful
and
develop progressive abnormalities of memory, cognition, orientation and behavior
Alzheimer’s
Describe: 3 stages
Alzheimer’s
-described in 3 stages, with a progressive pattern of cognitive and functional impairment.
The three stages are described as early or mild, middle or moderate, and late or severe.
The disease is known to target the hippocampus* which is *associated with memory, and this is responsible for the first symptoms of memory impairment.
As the disease progresses so does the degree of memory impairment
AD
First symptoms
The most noticeable deficit is short term memory loss, which shows up as difficulty in remembering recently learned facts and inability to acquire new information
Note: first symptoms are often mistakenly attributed to aging or stress. Detailed neuropsychological testing can reveal mild cognitive difficulties up to eight years* before a *person fulfills the clinical criteria for diagnosis of AD.
AD
Early stage:
In a small percentage, difficulties with language, executive functions, perception (agnosia), or execution of movements (apraxia) are more prominent than memory problems
Note: AD does not affect all memory capacities equally. Older memories of the person’s life (episodic memory), facts learned (semantic memory), and implicit memory (the memory of the body on how to do things, such as using a fork to eat or how to drink from a glass) are affected to a lesser degree than new facts or memories
AD
Middle stage:
Progressive deterioration hinders independence, unable to perform most common activities of daily living.
Speech difficulties due to an inability to recall vocabulary, leading to frequent incorrect word substitutions (paraphasias).
Reading and writing skills progressively lost, memory problems worsen, failure to recognise close relatives, Behavioral and neuropsychiatric changes
AD
Late stage:
patient is completely dependent upon caregivers
AD:
describe the involvement of APP:
APP (amyloid precursor protein) – NORMAL: neuron growth & repair; broken down into soluble peptide
- can be broken down insoluble amyloid beta which clumps together –>plaques
- plaques: - disrupt neuronal signalling
- initiate immune response -> inflammation ->neuronal damage
- deposit in brain vessels -> amyloid angiopathy
->↑risk of haemorrhage
Etiology of AD
Describe the attributes:
Only 1-2% of Alzheimer’s cases are inherited (autosomal dominant) = types are known as early onset familial Alzheimer’s disease, can have a very early onset, and a faster rate of progression.
Early onset familial AD can be attributed to mutations in one of three genes: those encoding amyloid-beta precursor protein (APP) and presenilins PSEN1 and PSEN2.
Most mutations in the APP and presenilin genes increase the production of a small protein called amyloid beta (Aβ)42, which is the main component of amyloid plaques
Alzheimer’s disease
is believed to occur when:
Alzheimer’s disease is believed to occur when abnormal amounts of amyloid beta, <em>accumulating extracellularly </em>as amyloid plaques**, and tau proteins, accumulating intracellularly as neurofibrillary tangles, form in the brain affecting neuronal functioning and connectivity, resulting in a progressive loss of brain function.
This altered protein clearance ability is age-related and is associated with other neurodegenerative diseases
AD
Tau protein function and neuronal loss:
- Tau protein* – NORMAL: keeps microtubules intact
- amyloid plaques outside the cell ->intracellular signalling -> phosphorylation of Tau-tangles
- tangles: - disrupt microtubulenon-functioning neuron, neuronal apoptosis
- neuronal loss can be: - loss of cholinergic neurons in nucleus basalis of Meynert (project to neocortex)
- in limbic system (hippocampus, parahippocampus)
AD:
2 Types
types:
- Sporadic – late onset, unknown causes, risk increases with age; 90-95% of cases!
- Familial – early onset, dominant gene mutations, speeds up disease progression
- PSEN-1, PSEN-2 mutations -> γ-secretase more likely to break down APP into β-amyloid
- also related to Trisomy 21 (Down syndrome)
AD
Symptoms:
- progressive dementia
(STM loss -> loss of some motor skills, language - >LTM loss -> disorientation)
- behavioural and psychological symptoms of dementia (BPSD) – in later stages
<strong><em>Note:</em></strong> “Behavioural and Psychological Symptoms of Dementia <strong><em>(BPSD)</em></strong>” refers to the spectrum of non-cognitive and non-neurological symptoms of dementia, such as agitation, aggression, psychosis, depression and apathy. At least 80% of people with dementiaexperience BPSD.
AD:
Diagnosis:
- mental status test
- exclusion of other causes of dementia (ie. head injury (esp. SDH), brain tumours, infections)
- CT, MRI
– neuronal death -> brain atrophy, narrowed gyri, wider sulci, enlarged ventricles
- definitive = brain biopsy (after death)
