neuropathology

• AMYLOID PRECURSOR PROTEIN IS ABNORMALLY CLEAVED
• Normal cleavage : Abeta 40 --> cannot aggregate
• Abnormal cleavage: Abeta 42 --> senile plaque

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.

accumulation of amyloid containing A4Beta.

Neurofibrillary tangles

Plaques

Neurofibrillary tangles (***correlate best with disease)

• Congophilic amyloid angiopathy   
• (cerebral amyloid angiopathy, CAA)‏

Granulovacuolar Degeneration of Simchowicz

SLOWLY EVOLVING DEMENTIA

PLAQUES AND AMYLOID ANGIOPATHY CONTAIN A4-Beta

NEUROFIBRILLARY TANGLES CONTAIN TAU PROTEIN

TANGLES CORRELATE WITH DZ

DEATH FROM PNEUMONIA, SEPSIS

• Rapidly progressive, fatal disorder that attacks neurons (brain, spinal) controlling
• voluntary muscles

Causes wasting of muscle resulting in respiratory failure

denervation atrophy

SOD1- antioxidant functions implicated in some familial forms.  TDP43 in sporadic ALS.

True

false

Rapidly progressive

Irreversible

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

Hypertension/Atherosclerosis

Coagulopathies (Blood thinners, liver failure, defective coagulation factors)‏

Saccular Aneurysms

Atherosclerosis, hypertension, and coagulopathies are important risk factors

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

HIGH GRADE

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.

• FALCINE
• Convexity
• WHORLS ARE TYPICAL OF MENINGIOMA
• Can be fibrous with much collagen

extraaxial

Glioblastoma- malignent -

Menigioma - often beign

Waxing and waning 

Sharply demarcated demyelinated plaques are typical (Axons are intact)

Dawson’s fingers

• autoimmune and Sharply
• demarcated demyelinated plaques are typical (Axons are intact

Dawson finger