Alzheimer’s disease

• Brain looks atrophic (thin gyri and widened sulci) – often see hydrocephalus ex vacuo

• Characteristic microscopic findings

  • Neurofibrillary tangles

    • Microtubular elements within neurons form a rigid structure

    • After the neuron dies these remain as evidence of the disease

    • Look like candle flames and are often called “flame cells”

  • Senile (AKA neuritic) plaques – extracellular material that’s mostly amyloid

  • Hirano bodies – intracytoplasmic crystalloid things

  • Granulovacuolar degeneration

  • Cerebral amyloid angiopathy

    • Amyloid deposits in blood vessels throughout the brain

    • Can become leaky and lead to intraparenchymal hemorrhage

  • None of the above are specific for AD, as all may be seen in a “normal” brain of an elderly person…what matters most is the number of these things seen (especially plaques)

• Diagnosis of AD

  • Can make presumptive diagnosis because of typical clinical course, but definitive diagnosis can only be made upon autopsy

  • Diagnosis made by counting number of plaques per filed and relating that to patient’s age

    • Diagnosis not based on number of tangles

    • Also not based on number of diffuse plaques (which are different than senile plaques)

  • Very difficult to tell early (low-grade) AD from normal aging

• Pathogenesis

  • Amyloid definitely plays a role based on the importance of amyloid precursor protein

    • APP is a normal, membrane-bound protein that is endocytosed and digestion (after digestion it is known as amyloid beta protein which is the bad one; it is the protein present in the amyloid angiopathy and neuritic plaques)

    • A mutation in the APP gene leads to early onset AD, which accounts for some of the familial cases of AD (familial only responsible for 5-10% of cases)

    • APP gene found on chromosome 21, so Down’s patients who live long enough will develop a progressive decline in mental function and will have pathologic features consistent with AD

  • Presensilins

    • Coded for on chromosomes 1 and 14

    • Somehow enhance the production of amyloid protein

    • Mutations increase risk for early AD onset

  • Apolipoprotein E4

    • Coded for on chromosome 19

    • Mutations lead to increased risk of early AD onset

  • Aluminum toxicity may play a role

  • Tau protein

    • Normal microtubular protein

    • One of the main proteins present in the neurofibrillary tangles

• CERAD designates certain brain foci as standard sections for AD diagnosis

  • Hippocampus and entorhinal cortex

  • Superior and medial gyri of the temporal lobe

  • Middle frontal gyrus of the frontal lobe

  • Inferior parietal lobe

  • Anterior cingulate gyrus (cortical Lewy bodies)

  • Midbrain

Category: Pathology Notes