Cortical atrophy, amyloid-predominant neuritic plaques, and tau-predominant neurofibrillary tangles are hallmarks of the pathological diagnosis of Alzheimer's disease and may be confirmed via postmortem histopathological examination. For early-onset cases with autosomal dominant inheritance, a mutation in one of the known causative Alzheimer's disease genes-amyloid precursor protein (APP), presenilin 1 (PSEN1), or presenilin 2 (PSEN2)- may be involved, and genetic testing for such mutations is commercially available, at least for PSEN1. Apolipoprotein E4 cannot serve as a diagnostic marker because it is only a risk factor and neither necessary nor sufficient for disease occurrence. Since amyloid beta-42 deposition in the brain occurs early in the pathophysiological cascade, amyloid-based diagnostic tests such as amyloid imaging on brain positron emission tomography (PET) scans and reduced levels of amyloid beta-42 in the cerebrospinal fluid (CSF) may have diagnostic value. Signs of neuronal injury, such as hippocampal and temporoparietal cortical atrophy on a magnetic resonance image scan, temporoparietal hypometabolism on a fluorodeoxyglucose PET scan, and evidence for elevated total tau and phospho-tau levels in CSF, provide evidence of neuronal damage but are less specific for Alzheimer's disease. At present, these biomarkers are not fully validated, and many are available only in tertiary care settings. However, some of them, along with novel biomarkers, will likely move into wider clinical practice in the coming years.🏁

Cortical atrophy, amyloid-predominant neuritic plaques, and tau-predominant neurofibrillary tangles are hallmarks of the pathological diagnosis of Alzheimer's disease and may be confirmed via postmortem histopathological examination. For early-onset cases with autosomal dominant inheritance, a mutation in one of the known causative Alzheimer's disease genes-amyloid precursor protein (APP), presenilin 1 (PSEN1), or presenilin 2 (PSEN2)- may be involved, and genetic testing for such mutations is commercially available, at least for PSEN1. Apolipoprotein E4 cannot serve as a diagnostic marker because it is only a risk factor and neither necessary nor sufficient for disease occurrence. Since amyloid beta-42 deposition in the brain occurs early in the pathophysiological cascade, amyloid-based diagnostic tests such as amyloid imaging on brain positron emission tomography (PET) scans and reduced levels of amyloid beta-42 in the cerebrospinal fluid (CSF) may have diagnostic value. Signs of neuronal injury, such as hippocampal and temporoparietal cortical atrophy on a magnetic resonance image scan, temporoparietal hypometabolism on a fluorodeoxyglucose PET scan, and evidence for elevated total tau and phospho-tau levels in CSF, provide evidence of neuronal damage but are less specific for Alzheimer's disease. At present, these biomarkers are not fully validated, and many are available only in tertiary care settings. However, some of them, along with novel biomarkers, will likely move into wider clinical practice in the coming years.🏁