Alzheimer's disease (AD) was first described by Alois Alzheimer in 1907, characterized by rapid memory loss and psychiatric disturbances in a 51-year-old woman. AD is a progressive neurological disorder with hallmark pathology, including senile plaques and neurofibrillary tangles (NFTs). Initially, AD was distinguished from senile dementia based on age of onset, but it is now recognized as a single entity with increasing prevalence after age 65. AD must be differentiated from other dementias, such as vascular dementia, Lewy body dementia, and frontotemporal dementia. Diagnosis requires clinical evidence of memory loss and impairment in at least one other cognitive domain, along with social or occupational dysfunction. While no reliable peripheral biochemical marker exists, definitive diagnosis requires histological examination of the brain at autopsy. Positron emission tomography (PET) using Pittsburgh Compound B (PiB) has shown conflicting results in detecting amyloid-β (Aβ) plaques, as PiB binding may not always differentiate symptomatic AD from asymptomatic controls. The concept of mild cognitive impairment (MCI) has been introduced to identify early neurodegenerative disease, but MCI is not a distinct entity and lacks a pathological substrate. AD pathology includes NFTs and senile plaques, with NFTs being more closely associated with clinical disease. The distinction between AD and aging pathology is complex, with NFTs and plaques showing varying distributions. AD pathology is also found in Down syndrome, supporting the amyloid cascade hypothesis. The Braak staging system describes the progression of NFTs from transentorhinal to isocortical regions, while the CERAD criteria focus on plaque pathology. The NIA-Reagan criteria classify AD cases into low, intermediate, and high likelihood based on pathology. Cerebral amyloid angiopathy (CAA) is a common condition in AD, with amyloid deposits in cerebral vessels. CAA is associated with vascular hemorrhage and may be linked to AD, but the relationship is complex. Aβ deposition in CAA is common in the elderly, and while Aβ is a risk factor for CAA, other factors such as APOE alleles also play a role. The role of Aβ in AD remains debated, with some studies suggesting that Aβ deposition is a homeostatic mechanism. Overall, AD is a progressive, incurable disease with significant clinical and economic implications.Alzheimer's disease (AD) was first described by Alois Alzheimer in 1907, characterized by rapid memory loss and psychiatric disturbances in a 51-year-old woman. AD is a progressive neurological disorder with hallmark pathology, including senile plaques and neurofibrillary tangles (NFTs). Initially, AD was distinguished from senile dementia based on age of onset, but it is now recognized as a single entity with increasing prevalence after age 65. AD must be differentiated from other dementias, such as vascular dementia, Lewy body dementia, and frontotemporal dementia. Diagnosis requires clinical evidence of memory loss and impairment in at least one other cognitive domain, along with social or occupational dysfunction. While no reliable peripheral biochemical marker exists, definitive diagnosis requires histological examination of the brain at autopsy. Positron emission tomography (PET) using Pittsburgh Compound B (PiB) has shown conflicting results in detecting amyloid-β (Aβ) plaques, as PiB binding may not always differentiate symptomatic AD from asymptomatic controls. The concept of mild cognitive impairment (MCI) has been introduced to identify early neurodegenerative disease, but MCI is not a distinct entity and lacks a pathological substrate. AD pathology includes NFTs and senile plaques, with NFTs being more closely associated with clinical disease. The distinction between AD and aging pathology is complex, with NFTs and plaques showing varying distributions. AD pathology is also found in Down syndrome, supporting the amyloid cascade hypothesis. The Braak staging system describes the progression of NFTs from transentorhinal to isocortical regions, while the CERAD criteria focus on plaque pathology. The NIA-Reagan criteria classify AD cases into low, intermediate, and high likelihood based on pathology. Cerebral amyloid angiopathy (CAA) is a common condition in AD, with amyloid deposits in cerebral vessels. CAA is associated with vascular hemorrhage and may be linked to AD, but the relationship is complex. Aβ deposition in CAA is common in the elderly, and while Aβ is a risk factor for CAA, other factors such as APOE alleles also play a role. The role of Aβ in AD remains debated, with some studies suggesting that Aβ deposition is a homeostatic mechanism. Overall, AD is a progressive, incurable disease with significant clinical and economic implications.