Volume 7 Issue 9 September, 2017
Consultation Liaison Psychiatry Neuro-pathology
Alzheimer Disease (AD) is the most common cause of dementia accounting for 60- 80% of dementia cases in elderly. It manifests as an insidious impairment of higher intellectual functions, with alterations in mood & behavior to progressive memory loss, aphasia and finally leading to disabled, mute, and immobile.
Acetylcholine seems to be particularly important for memory; loss of cholinergic neurons in Alzheimer’s disease underlies the memory impairment. The key abnormality in AD is the deposition of Aβ peptides, which are derived through amyloidogenic processing of Amyloid Precursor Protein (APP) which is a cell surface protein. Aβ aggregate into small oligomere which are toxic and cause neuronal dysfunction. The Aβ eventually form large aggregates and fibrils.
Grossly, there is diffuse cortical atrophy with compensatory ventricular enlargement. Microscopically, two characteristic findings include the neuritic plaques and neurofibrillary tangles. Plaques are extracellular spherical structures with a core of Aβ amyloid surrounded by a halo and a ring of dystrophic neurites measuring around 20 to 200 μm in diameter. Neurofibrillary tangles are insoluble twisted helical filaments found inside the cell body and dendrites of neuron and composed of abnormally hyperphosphorylated tau protein which forms part of a microtubule. In AD, however, the tau protein is abnormal and the microtubule structures collapse. Plaques are assessed semi -quantitatively in each cortical area, while tangles are assessed based on how widespread they are in the brain.
Other features include granulovacuolar degeneration and hirano bodies. Granulovacuolar degeneration is a small intraneuronal cytoplasmic vacuole containing an argyrophilic granule which is seen in abundance at hippocampus and olfactory bulb area. Hirano bodies are described as elongated, glassy, eosinophilic bodies containing beaded actin filaments, found within the hippocampal region. Cerebral amyloid angiopathy changes are usually seen in AD.
All the above pathologic changes start in the entorhinal cortex, spreading to the hippocampus & finally extending into the neocortex.
Tau immunostain and silver stains (Bielschowsky and Gallyas) identify neuritic plaques & tangles, there by aid in the diagnosis of AD.
Dr. Shruthi N. Shetageri, Assistant Professor, Dept. of Pathology, MVJMC & RH, Hoskote, Bengaluru
