Alzheimer disease (AD) is a neurodegenerative disorder characterized by β-amyloid (Aβ)-containing extracellular plaques and tau-containing intracellular neurofibrillary tangles. AD typically presents with prominent amnestic cognitive impairment but can also manifest as non-amnestic cognitive impairment. The severity of cognitive impairment varies, with mild cognitive impairment (MCI) being the earliest symptomatic stage, followed by dementia. AD is a common cause of cognitive impairment in midlife and late life, but its clinical impact is modified by other neurodegenerative and cerebrovascular conditions. AD biology involves a complex interplay of synaptic homeostasis loss and dysfunction in endosomal/lysosomal clearance pathways. Therapeutic efforts struggle to find targets that substantially change the clinical course of AD. AD is associated with various risk factors, including age, APOE ε4 allele, and modifiable factors such as diabetes, hypertension, and smoking. The pathology of AD involves Aβ-containing plaques and tau-containing neurofibrillary tangles, with Aβ and tau playing critical roles in synaptic dysfunction and neurodegeneration. Aβ is derived from the amyloid precursor protein (APP) through cleavage by β- and γ-secretases, while tau is a microtubule-associated protein that becomes hyperphosphorylated and aggregates in AD. APOE ε4 increases the risk of AD, and other genetic variants may contribute to AD risk. Dysfunctional proteostasis, including impaired lysosomal function and autophagy, contributes to AD pathology. AD is a synaptic dysfunction disorder involving molecular, cellular, and macro-scale cortical circuitry failures. Synaptic loss is strongly correlated with cognitive impairment in AD, and Aβ and tau pathology are linked to synaptic dysfunction. The clearance of Aβ and tau is impaired in AD, leading to neurodegeneration. Aβ and tau pathology are associated with distinct patterns of brain atrophy and cognitive impairment. Imaging biomarkers such as Aβ-PET and FDG-PET are used to diagnose and stage AD, with Aβ-PET providing direct visualization of Aβ plaque accumulation. Biomarkers such as CSF Aβ42 and Aβ-PET are closely but inversely correlated. AD diagnosis involves clinical evaluation, biomarkers, and imaging, with the goal of identifying AD pathology and distinguishing it from other neurodegenerative conditions. The management of AD involves addressing cognitive impairment and improving quality of life for patients and their caregivers.Alzheimer disease (AD) is a neurodegenerative disorder characterized by β-amyloid (Aβ)-containing extracellular plaques and tau-containing intracellular neurofibrillary tangles. AD typically presents with prominent amnestic cognitive impairment but can also manifest as non-amnestic cognitive impairment. The severity of cognitive impairment varies, with mild cognitive impairment (MCI) being the earliest symptomatic stage, followed by dementia. AD is a common cause of cognitive impairment in midlife and late life, but its clinical impact is modified by other neurodegenerative and cerebrovascular conditions. AD biology involves a complex interplay of synaptic homeostasis loss and dysfunction in endosomal/lysosomal clearance pathways. Therapeutic efforts struggle to find targets that substantially change the clinical course of AD. AD is associated with various risk factors, including age, APOE ε4 allele, and modifiable factors such as diabetes, hypertension, and smoking. The pathology of AD involves Aβ-containing plaques and tau-containing neurofibrillary tangles, with Aβ and tau playing critical roles in synaptic dysfunction and neurodegeneration. Aβ is derived from the amyloid precursor protein (APP) through cleavage by β- and γ-secretases, while tau is a microtubule-associated protein that becomes hyperphosphorylated and aggregates in AD. APOE ε4 increases the risk of AD, and other genetic variants may contribute to AD risk. Dysfunctional proteostasis, including impaired lysosomal function and autophagy, contributes to AD pathology. AD is a synaptic dysfunction disorder involving molecular, cellular, and macro-scale cortical circuitry failures. Synaptic loss is strongly correlated with cognitive impairment in AD, and Aβ and tau pathology are linked to synaptic dysfunction. The clearance of Aβ and tau is impaired in AD, leading to neurodegeneration. Aβ and tau pathology are associated with distinct patterns of brain atrophy and cognitive impairment. Imaging biomarkers such as Aβ-PET and FDG-PET are used to diagnose and stage AD, with Aβ-PET providing direct visualization of Aβ plaque accumulation. Biomarkers such as CSF Aβ42 and Aβ-PET are closely but inversely correlated. AD diagnosis involves clinical evaluation, biomarkers, and imaging, with the goal of identifying AD pathology and distinguishing it from other neurodegenerative conditions. The management of AD involves addressing cognitive impairment and improving quality of life for patients and their caregivers.