Alzheimer’s disease

on 28.1.09 with 0 comments

  • 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



Post a Comment