Alzheimer's Flashcards
Dementia
General loss of global cognitive ability
Not a disease–symptom of many diseases
Alzheimer’s
Average age of onset--65 Early onset--45-50 yrs Currently 30 million patients worldwide 2050: 1 in 85 people will have the disease--as people become older, it is more likely to develop Age related disease One of the most costly diseases
Pre-dementia
Mild cognitive difficulties, very short term memory loss
Early dementia
Increased impairment of learning and memory
Still retain long-term memory
Loss of vocabulary–writing and speaking becomes difficult
Moderate dementia
Difficult to perform day-to-day tasks
Increase loss in memory (won’t recognize people)
Disorientation of time and space (leads to confusion and wandering)
Sundowning–as sun sets, patients have more severe symptoms
Late dementia
Loss of long term memories
Loss of movement and exhaustion
Aging brain v. Early dementia
Non Alzheimer’s brain–occasional forgetfulness, minor short term memory loss
Early Alzheimer’s–general state of absentmindedness, word and names, recognition of names and people, confusion to new situations
Diagnosing dementia
No scans or blood tests
Mental exams–Mini Mental State Exam, Abbreviated Mental Test Score, Trail Making Test
The Alzheimer’s brain
Significant degeneration of specific regions of the brain (hippocampus–responsible for short term memory)
3 Alzheimer’s hypotheses
- Cholinergic hypothesis
- Senile plaques
- Tangles
Cholinergic hypothesis
Alzheimer’s hypothesis
Alzheimer’s patients display extremely low levels of acetylcholine
First class of drugs are developed–increase levels of acetylcholine
Senile plaques
Alzheimer’s hypothesis
Extracellular plaques
Dense material outside of cell
Appear in normally aged brain–significantly more in Alzheimer’s patients
a) plaques are made of proteins–what proteins?
Down’s syndrome patients have extra copy of chromosome 21–more senile plaques, leads to Alzheimer’s; protein on chromosome 21 leads to Alzheimer’s
b) more plaques–higher degree of dementia
Amyloid B precursor protein (APP)
Protein on chromosome 21 that leads to Alzheimer’s
Found at cell surface
Concentrated in synapses
Essential for normal brain development
Normally cut by secretases: enzymes that regulate other proteins by cutting them
Secretases
enzymes that regulate other proteins by cutting them
AB
39-42 amino acid fragment of APP
Makes up amyloid plaques in brain
40 amino acids is more common and is nontoxic–cell can easily remove it
42 amino acids more easily forms fibers and plaques
Late Alzheimer’s–AB fibers aggregate and become insoluble, resulting in plaques
How do extracellular plaques lead to disease?
Long term potentiation
Early Alzheimer’s–block synaptic transmission; inhibits pathways that turn on new gene synthesis
Tangles
Alzheimer’s hypothesis
Intercellular protein TAU inside of neurons
TAU binds to microtubules and maintain highways
Aggregated TAU cUses breakdown and traffic jams
Early onset Alzheimer’s
Rare–10% of all Alzheimer’s patients
Before age 65 (45-69)
Familial Alzheimer’s disease–specific mutations that are inherited (ex: presenilin 1 and 2(gamma secretase), APP)
Genetic risk factors
15 genes linked to increased likelihood
ApoE–transports cholesterol to neurons; aids in removal of AB peptides
40-80% of Alzheimer’s cases have ApoE mutations
Diagnosing Alzheimer’s
8 cognitive domains impaired–quiz
Brain imaging–PET scan
Visualizing Alzheimer’s
- Dye that CAT or MRI can see
- Cross blood brain barrier
- Bind to amyloid deposits
Pittsburg B Compound (PiB)
Florbetapir
Alzheimer’s treatments
Pharmaceuticals
Vaccines against amyloid aggregates
Chaperone proteins –HSP100
Prevention
No cure but we can prevent Alzheimer's Diet/nutrition Stress management Exercise Medication--NSAID, cholesterol reduction Learning Lifestyle--playing games, musical instruments, regular social interaction
