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Seven centres showed a high correlation with the new Gothenburg measurements; therefore, 10 cohorts from these centres are included in the analyses here (1233 healthy control subjects, 40-84 years old). Amyloid-β amyloid status (negative or positive) and neurodegeneration status (negative or positive) was established based on the pathological cerebrospinal fluid Alzheimer's disease cut-off values for cerebrospinal fluid amyloid-β1-42 and total tau, respectively. While gender did not affect these biomarker values, APOE genotype modified the age-associated changes in cerebrospinal fluid biomarkers such that APOE ε4 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-β1-42 values and APOE ε2 carriers showed the opposite effect. At 40 years of age, 76% of the subjects were classified as amyloid negative, neurodegeneration negative and their frequency decreased to 32% at 85 years. The amyloid-positive neurodegeneration-negative group remained stable. The amyloid-negative neurodegeneration-positive group frequency increased slowly from 1% at 44 years to 16% at 85 years, but its frequency was not affected by APOE genotype. The amyloid-positive neurodegeneration-positive frequency increased from 1% at 53 years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-β1-42 levels were already frequent in midlife and APOE genotype strongly affects the levels of cerebrospinal fluid amyloid-β1-42, phosphorylated tau and total tau across the lifespan without influencing the frequency of subjects with suspected non-amyloid pathology.","is_dataset_classified":null,"base_score":4.969813299576001,"endowment":4.969813299576001,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26220940","pmcid":"PMC4643624","openalex_id":"https://openalex.org/W1825683130","authors":[],"funders":[{"funder_name":"NIA NIH HHS","grant_id":"AG1210","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R21 AG043885","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"P50 NS053488","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL118624","title":null},{"funder_name":"NCATS NIH HHS","grant_id":"UL1 TR001079","title":null},{"funder_name":"NIA 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