The two hallmark pathologies required for a diagnosis of Alzheimer&;s disease(AD) are the extracellular plaque deposits of the Beta-amyloid peptide (Ab) and the intracellular flame-shaped neurofibrillary tangles of the Hyper-Phophorylated microtubule binding protein &;tau&;. Histological Hallmarks of Alzheimer&;s disease: b-Amyloid Plaque (Extracellular) Neurofibrillary Tangles (Intracellular) b-Amyloid Neuritic plaques are formed by extracellular accumulation of beta amyloid deposits. &;Neuritic&; or &;Senile&; b-amyloid plaques are an early histopathological sign of Alzheimer&;s disease (that occur rarely in healthy subjects) The amyloid b-protein accumulated in single Neuritic plaques is toxic to surrounding structures and adjacent neurons. Clinico-pathological studies have shown that amyloid burden does not directly correlate with severity or duration of dementia. Neurofibrillary tangles are formed by intracellular accumulation of hyper-phophorylated microtubule binding protein &;tau&; NFT&;s occur in many neurodegenerative diseases and/or a group of diseases called &;taupathies&;. These include Frontotemporal dementia, Pick&;s disease etc., The co-occurence of b-amyloid plaques with NFT&;s suggests a diagnosis of Alzheimer&;s disease (AD) The NFT&;s are toxic to the neurons and neurons with NFT&;s eventually die and degnerate leaving a residual &;ghost tangle&; in the extramedullary space reminding of the pyramidal cell body in which it was initially formed. Clinico-pathological studies have shown that dementia correlates more strongly with NFT&;s than with senile plaques (b-Amyloid) Ref: Bailey and Love 27th edition