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- AMYLOID PRECURSOR PROTEIN IS ABNORMALLY CLEAVED
- Normal cleavage : Abeta 40 --> cannot aggregate
- Abnormal cleavage: Abeta 42 --> senile plaque
Genes associated with Alzheimers
Amyloid precursor protein (APP)
Presenilin 1, presenilin 2 (early onset)
E4 allele of apolipoprotein E
- Genetic or acquired defects in APP processing result in accumulation of amyloid
- containing A4Beta.
- ? Amyloid is a primary or secondary event.
- Amyloid plaques and cerebral amyloid angiopathy.
Neurofibrillary tangles- Paired helical filaments with hyperphosphorylated tau in neurons.
In Alzheimer, Genetic or acquired defects in APP processing result in
accumulation of amyloid containing A4Beta.
In Alzheimer, Paired helical filaments with hyperphosphorylated tau in neurons.
Alzheimer's 4 features
(***correlate best with disease)
- Congophilic amyloid angiopathy
- (cerebral amyloid angiopathy, CAA)
Granulovacuolar Degeneration of Simchowicz
ALZHEIMER DISEASE - what is it, its etiology, its microscopic presentation, cause of death
SLOWLY EVOLVING DEMENTIA
PLAQUES AND AMYLOID ANGIOPATHY CONTAIN A4-Beta
NEUROFIBRILLARY TANGLES CONTAIN TAU PROTEIN
TANGLES CORRELATE WITH DZ
DEATH FROM PNEUMONIA, SEPSIS
Amyotrophic Lateral Sclerosis
- Rapidly progressive, fatal disorder that attacks neurons (brain, spinal) controlling
- voluntary muscles
Causes wasting of muscle resulting in respiratory failure
ALS- results in
ALS - genetic component
SOD1- antioxidant functions implicated in some familial forms. TDP43 in sporadic ALS.
True or false
Elevated glutamate (neurotransmitter toxicity) may mediate ALS
True or False
In ASL, the disease affects both muscle and sensory fxn because of the demylination
Definition of Stroke
Non-convulsive neurologic deficit >24 hr
- 70-80% from infarcts and 20-30% from
- hemorrhages in Western world
Includes cerebral infarcts and hemorrhages
- Cerebral infarcts (localized injury related to ischemia/hypoxia) include thrombotic,
- embolic, and hemorrhagic reperfusion injuries
This is a transient ischemic attack in which neurologic symptoms are from transient vascular obstruction. < 24 hrs
1/3 of TIA patients will have significant infarcts in 5 years
F= FACE Ask them to smile. Does one side droop?
- A= ARMS Ask to raise both arms. Does
- one arm drift downward?
S= SPEECH Ask the person to repeat a simple phrase. Does the speech sound strange or slurred?
T= TIME See any of these signs. Time to CALL 911.
Local interruption of blood flow
Risk factors: 70 yo, male, atherosclerosis (hypertension, diabetes, smoking)
Thrombosis in atherosclerotic vessels
Emboli from heart or atherosclerotic vessels
Extensive vascular anastomoses in the Circle of Willis may mitigate a stroke
Edema maximal at 3-4 days
Cystic and liquified by 6 months
Coagulopathies (Blood thinners, liver failure, defective coagulation factors)
STROKE - risk factor
Atherosclerosis, hypertension, and coagulopathies are important risk factors
Stroke - causes
Hemorrhage and infarct
Prevalence: 360,000 primary brain tumors
Most common intraaxial/intrinsic brain tumor is glioblastoma
Most common extraaxial/meninges-based tumor is meningioma
MEDIAN SURVIVAL: 1 year
AGGRESSIVE INFILTRATIVE INTRAXIAL (PARENCHYMAL) TUMOR
Most common is meningioma
A tumor derived from arachnoidal cells
Mostare benign- slow growing. Grade I can recur. Some are aggressive and can metastasize distantly.
Brain tumor morphology
- WHORLS ARE TYPICAL OF MENINGIOMA
- Can be fibrous with much collagen
Intraaxial vs extraaxial: which one is better to cure
BRAIN TUMOR's intraaxial
Glioblastoma- malignent -
Brain tumor - extraaxial
Menigioma - often beign
In Multiple Sclerosis, The neurologic symptom progress
Waxing and waning
Sharply demarcated demyelinated plaques are typical (Axons are intact)
Multiple Sclerosis is probably caused by
- autoimmune and Sharply
- demarcated demyelinated plaques are typical (Axons are intact
MS's brain scan presentation
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