Parkinson and Alzheimer Flashcards
PD and AD are both examples of
primary neurodegenerative diseases
dementia disorders
primary vs secondary neurodegenerative diseases
primary - death intrinsic on cell, do not know how to stop cell death
secondary - response to something else (ex. polio, siphilus)
dementia disorders
serious loss of cognition - ability to think and rationalize your surroundings
Is acquired - chronic, progressive, is a syndrome (collection/spectrum of symptoms)
progressive neurodegenerative diseases
Progressive destruction of nerve cells → death
Elderly grew forgetful → senile dementia
Various types of dementia, some treatable
Rising evidence that many are a type of prion disease
Accumulation of protein “plaques”
Nerve cell necrosis
Gliosis → activation of astrocytes, microglia
Most common form of dementia
Alzheimer’s
Amyloidosis, tauopathy
Alzheimer’s First described in 1906 by
psychiatrist Alois Alzheimer
AD patient zero
51 year-old suffering from severe dementia
Described the symptoms and the pathological manifestations
Extracellular deposits of a “peculiar substance” → amyloids
Intracellular fibrillary bundles → tau tangles
In 1976 AD accepted to be the cause of most
senile dementias
was considered to be a rare form of early- onset AD - more autopises showed was more common
AD hypothesis was confirmed when
rare mutation were discovered in chromosome 21 (contains APP gene)→ explained incidence of dementia in Down syndrome (b/c have more of amaloid-b gene)
nodding syndrome
____ mutations have been linked to AD since
> 50 APP
AD incidence in US
5 % of adults > 65
30 – 40 % of adults > 85
Top cauzes of death in high vs low income countries
Disproportionally prevalent in “developed” world - US and EU
AD incidence groups
Woman almost 2X more likely
- Framingham study since 1948 → still ongoing
African American woman > 5X
- Possibly due to diabetes (a risk factor for AD)
____ seems to be protective (AD)
Education
brain activity? Or just socioeconomic status?
also potential reason for women more likely - 40s and 50s were not allowed to study (even more so african american women)
____ of AD patients start with ____
> 75 %
memory problems
early - miss place things, issue with short term memory - not issue with long term memory yet
Motor functions spared until very late in AD
As AD progresses symptoms
(MM AL) Language, Mood, Memory, Activities
Language becomes less fluid, comprehension declines - other cogantive functions decline
Mood changes common: mild depression and social withdrawal - avoid people because cannot remember them
Memory loss more pervasive, involving older memories
Severely interfere with normal activities, i.e. driving
Problems walking, eating, taking care of themselves → economic and psychological burden on caregivers
Capgras syndrome
think people replaced by identical impostors
similar to psychosis - trying to make justify things with ideas
AD Onset to death
8 – 10 years
types of dementia
cortical (AD)
or subcortical (PD)
AD MRI
black spaces - cell death
white spaces - inflammation
key difference with prion disease (no inflammation)
AD classic example of
cortical
Loss of the cerebral cortex
Cell necrosis
“Senile plaques” → amyloid-β
AD tangles → hyperphosphorylated tau protein
Immune reaction to plaques → damaging inflammation (chronic)
Impaired clearance of wastes (white build up on capilaries - should be removed but not)
“Senile plaques”
→ amyloid-β
AD tangles
→ hyperphosphorylated tau protein
Cellular issues in AD
Neuronal transport system is disrupted by tau tangles
- Less neurotransmitters, and other components, are delivered to synapses
Axon destruction
Plaques act as catalysts - dissemination/spread of AD
Plaques elicits inflammatory response -Neuron killing
AD treatments
There are 4 FDA approved drugs → none is a cure
3 of them are inhibitors of cholinesterase → increases neurotransmitter availability [problem - not take NT to synapse, help by inc NT levels at synapse]
NMDA receptor antagonist → NMDA involved in learning, also allows glutamate import → glutamate toxicity
(enzyme → inhibitor
receptor → antagonist)
(some treatment uses both types)
AD Early diagnosis is key, but problematic because
finding volunteers at ever- earlier stages of disease - hard - difficult to research
Research targeting the clearance of plaques promising → learning from prion research! (monoclonal antibody)
Second most common progressive neurodegnerative diease
PD
PD Described in 1817 as
“Shaking Palsy”
3 classical symptoms of PD
Tremors
abnormal posture and gait
reduced muscle strength
PD cortical vs subcortical
subcortical dementia - degeneration of the “substantia nigra” (in brain stem) neurons that produce a black pigment (DA producing)
PD is thought to be a consequence of
genetics and environment
Up to 25 % of patients have a relative affected as well
Incidence of PD
PD more common in men than women Caucasians 3X more likely
Typical onset of PD
> 65 years-old
very rare early onset cases - purely genetic cases (7 genes involved so far)
_____ are the earliest symptoms of PD
Tremors
are autorecognized - recognized by patient - first one to notice
Other symptoms of PD
(MMM O) Motion, mood, dementia(memory), olfaction
PD is Very well studied
oldest movement disorders identified, but also many celebrities with PD (Muhammad Ali or Michael J. Fox)
synucleinopathy
synucleinopathy - exhibit Lewy bodies
PD is one of many
role in PD unclear - seems to be involved in propagation/spread over brain
PD diagnositic
levadopa - DA precursor -if take and helps confirms PD disgnosis
α-synuclein in PD
Lewy bodies → aggregates of α-synuclein → late stages → dementia
The main causative pathology in PD is
death of dopaminergic neurons
What kills DA neurons in PD? Why just them? Why other neurons are spared?
PD treatments
Are plaques cause or consequence
