Alzheimer disease (AD) is characterized by the accumulation of proteins, neuronal and synaptic loss, and reactive processes. Extracellular amyloid-beta (Aβ) accumulates in the brain parenchyma as diffuse, focal, or stellate deposits, often involving vessel walls. Aβ deposition follows a stepwise progression, and tau accumulation, a key histopathological correlate of clinical symptoms, occurs in three forms: neurofibrillary tangles in cell bodies, neuropil threads in dendrites, and neuritic corona in axons. Tau pathology progresses from the entorhinal cortex through the hippocampus to the isocortex. Neuronal loss is heterogeneous and area-specific, with the timing of synaptic loss still debated. Various clinico-pathological types of AD have been described based on lesion types, onset, cause, and associated lesions. AD pathology is divided into three categories: accumulation-related lesions (positive), loss-related lesions (negative), and reactive processes (inflammation and plasticity). Accumulation-related lesions include Aβ and tau deposits, which are abnormal and poorly soluble. Aβ is produced by cleaving the amyloid precursor protein (APP) and cleared by enzymes like neprilysin and insulin-degrading enzyme. Aβ oligomers may be toxic and interact with glutamate receptors, affecting synaptic function. Aβ is cleared through interstitial fluid and the Virchow-Robin space, and crosses the blood-brain barrier via LRP-1 or P-glycoprotein. Aβ deposits are classified as diffuse, focal, or stellate, with "senile plaque" being a term with ambiguous meaning. Aβ deposits are associated with proteins like ApoE and ApoJ, and may contain cholesterol. The role of Aβ and tau in AD remains unclear, but their accumulation is central to the disease's pathology.Alzheimer disease (AD) is characterized by the accumulation of proteins, neuronal and synaptic loss, and reactive processes. Extracellular amyloid-beta (Aβ) accumulates in the brain parenchyma as diffuse, focal, or stellate deposits, often involving vessel walls. Aβ deposition follows a stepwise progression, and tau accumulation, a key histopathological correlate of clinical symptoms, occurs in three forms: neurofibrillary tangles in cell bodies, neuropil threads in dendrites, and neuritic corona in axons. Tau pathology progresses from the entorhinal cortex through the hippocampus to the isocortex. Neuronal loss is heterogeneous and area-specific, with the timing of synaptic loss still debated. Various clinico-pathological types of AD have been described based on lesion types, onset, cause, and associated lesions. AD pathology is divided into three categories: accumulation-related lesions (positive), loss-related lesions (negative), and reactive processes (inflammation and plasticity). Accumulation-related lesions include Aβ and tau deposits, which are abnormal and poorly soluble. Aβ is produced by cleaving the amyloid precursor protein (APP) and cleared by enzymes like neprilysin and insulin-degrading enzyme. Aβ oligomers may be toxic and interact with glutamate receptors, affecting synaptic function. Aβ is cleared through interstitial fluid and the Virchow-Robin space, and crosses the blood-brain barrier via LRP-1 or P-glycoprotein. Aβ deposits are classified as diffuse, focal, or stellate, with "senile plaque" being a term with ambiguous meaning. Aβ deposits are associated with proteins like ApoE and ApoJ, and may contain cholesterol. The role of Aβ and tau in AD remains unclear, but their accumulation is central to the disease's pathology.