Alzheimer disease (AD) is characterized by neuropathological features including "positive" lesions such as amyloid plaques, cerebral amyloid angiopathy, neurofibrillary tangles, and glial responses, and "negative" lesions such as neuronal and synaptic loss. Postmortem studies have enabled the staging of AD pathology and the development of diagnostic criteria. Clinicopathological correlations have helped establish a continuum between normal aging and AD dementia, showing that amyloid plaque accumulation occurs before cognitive deficits, while neurofibrillary tangles, neuron loss, and synaptic loss parallel cognitive decline. These findings are supported by longitudinal in vivo studies using imaging biomarkers like amyloid PET and volumetric MRI. Neuropathological changes in AD include both positive and negative features. Positive lesions include amyloid plaques, neurofibrillary tangles, neuropil threads, and dystrophic neurites. Negative features include neuronal and synaptic loss. Amyloid plaques are classified as diffuse or dense-core based on morphology and staining. Dense-core plaques are associated with synaptic loss and glial activation. Cerebral amyloid angiopathy (CAA) is a common feature, with amyloid β accumulating in vessel walls. Amyloid β is a peptide derived from the amyloid precursor protein, and its accumulation forms plaques and fibrils associated with AD pathology. Neurofibrillary tangles (NFTs) consist of hyperphosphorylated tau, forming paired helical filaments. NFTs progress in a stereotypical pattern, starting in the entorhinal cortex and spreading to the hippocampus and isocortex. They are associated with cognitive decline and are used in AD diagnosis. Amyloid plaques are classified as diffuse or dense-core, with dense-core plaques associated with neurotoxic effects. CAA is a common feature in AD, with amyloid β accumulating in vessel walls, potentially causing hemorrhages. Clinicopathological correlations show that NFT burden correlates with dementia severity and progression. Amyloid burden does not always correlate with dementia severity, but overall amyloid accumulation increases with disease progression. CAA is often present in AD patients, contributing to cognitive decline. Granulovacuolar degeneration and Hirano bodies are common in AD, with unclear origins but potential roles in tangle formation and apoptosis. Glial responses, including reactive astrocytes and activated microglial cells, are associated with dense-core plaques. Neuronal loss is a major component of cortical atrophy, with synapse loss also contributing to cognitive decline. Synapse loss precedes neuronal loss and is a better correlate of cognitive deficits than NFT burden. Pathological criteria for AD diagnosis rely on amyloid plaques and NFTs. The NIA-RI consensus criteria combine CERAD scores and Braak staging to classify AD with high, intermediate, or low likelihood. Mild cognitive impairment (MCI) is a transitional stage between normal agingAlzheimer disease (AD) is characterized by neuropathological features including "positive" lesions such as amyloid plaques, cerebral amyloid angiopathy, neurofibrillary tangles, and glial responses, and "negative" lesions such as neuronal and synaptic loss. Postmortem studies have enabled the staging of AD pathology and the development of diagnostic criteria. Clinicopathological correlations have helped establish a continuum between normal aging and AD dementia, showing that amyloid plaque accumulation occurs before cognitive deficits, while neurofibrillary tangles, neuron loss, and synaptic loss parallel cognitive decline. These findings are supported by longitudinal in vivo studies using imaging biomarkers like amyloid PET and volumetric MRI. Neuropathological changes in AD include both positive and negative features. Positive lesions include amyloid plaques, neurofibrillary tangles, neuropil threads, and dystrophic neurites. Negative features include neuronal and synaptic loss. Amyloid plaques are classified as diffuse or dense-core based on morphology and staining. Dense-core plaques are associated with synaptic loss and glial activation. Cerebral amyloid angiopathy (CAA) is a common feature, with amyloid β accumulating in vessel walls. Amyloid β is a peptide derived from the amyloid precursor protein, and its accumulation forms plaques and fibrils associated with AD pathology. Neurofibrillary tangles (NFTs) consist of hyperphosphorylated tau, forming paired helical filaments. NFTs progress in a stereotypical pattern, starting in the entorhinal cortex and spreading to the hippocampus and isocortex. They are associated with cognitive decline and are used in AD diagnosis. Amyloid plaques are classified as diffuse or dense-core, with dense-core plaques associated with neurotoxic effects. CAA is a common feature in AD, with amyloid β accumulating in vessel walls, potentially causing hemorrhages. Clinicopathological correlations show that NFT burden correlates with dementia severity and progression. Amyloid burden does not always correlate with dementia severity, but overall amyloid accumulation increases with disease progression. CAA is often present in AD patients, contributing to cognitive decline. Granulovacuolar degeneration and Hirano bodies are common in AD, with unclear origins but potential roles in tangle formation and apoptosis. Glial responses, including reactive astrocytes and activated microglial cells, are associated with dense-core plaques. Neuronal loss is a major component of cortical atrophy, with synapse loss also contributing to cognitive decline. Synapse loss precedes neuronal loss and is a better correlate of cognitive deficits than NFT burden. Pathological criteria for AD diagnosis rely on amyloid plaques and NFTs. The NIA-RI consensus criteria combine CERAD scores and Braak staging to classify AD with high, intermediate, or low likelihood. Mild cognitive impairment (MCI) is a transitional stage between normal aging