BACKGROUND: Low amyloid β42 (Aβ42) and high total tau and phosphorylated tau (p-tau) concentrations in the cerebrospinal fluid (CSF) are biomarkers of Alzheimer's disease (AD), reflecting brain deposition of amyloid plaques and tangles. Age and apolipoprotein E allele E4 are two strong risk factors for AD, but few data are still available on their effect on CSF markers in normal aging. OBJECTIVE: To study the effect of age on CSF Aβ42, total tau, and p-tau levels in a well-characterized group of cognitively normal subjects. METHODS: CSF Aβ42 levels of 81 subjects (27% female, 53 ± 15.3 years, range: 21-88) were determined with sandwich enzyme-linked immunosorbent assay; of these, total tau and p-tau levels were measured in 61 (75%) and 42 (52%) cases, respectively. A linear regression analysis between age and CSF markers was carried out on the whole sample and separately in apolipoprotein E allele ɛ4 carriers and noncarriers. RESULTS: The median levels of all markers were significantly different between young (<65 years) and old (≥65 years) subjects (Aβ42: P = .03; tau: P = .02; p-tau: P = .002; tau/Aβ42: P = .004; p-tau/Aβ42: P = .03). The association of marker levels with age was confirmed in linear regression models, where a positive relationship with age was observed for total tau (B = 2.3; 95% confidence interval [CI]: 0.89 to 3.7; P = .002), p-tau (B = 0.5; 95% CI: 0.1 to 0.9; P = .02), and tau/Aβ42 ratio (B = 0.006; 95% CI: 0.002 to 0.01; P = .002). No subjects showed abnormal tau, whereas 19% showed abnormal CSF Aβ42 concentrations. CONCLUSION: In cognitively normal subjects, the concentrations of CSF biomarkers of AD are associated with age. Further longitudinal studies could clarify whether Aβ42 low levels represent a preclinical AD biomarker.
BACKGROUND: Low amyloid β42 (Aβ42) and high total tau and phosphorylated tau (p-tau) concentrations in the cerebrospinal fluid (CSF) are biomarkers of Alzheimer's disease (AD), reflecting brain deposition of amyloid plaques and tangles. Age and apolipoprotein E allele E4 are two strong risk factors for AD, but few data are still available on their effect on CSF markers in normal aging. OBJECTIVE: To study the effect of age on CSF Aβ42, total tau, and p-tau levels in a well-characterized group of cognitively normal subjects. METHODS: CSF Aβ42 levels of 81 subjects (27% female, 53 ± 15.3 years, range: 21-88) were determined with sandwich enzyme-linked immunosorbent assay; of these, total tau and p-tau levels were measured in 61 (75%) and 42 (52%) cases, respectively. A linear regression analysis between age and CSF markers was carried out on the whole sample and separately in apolipoprotein E allele ɛ4 carriers and noncarriers. RESULTS: The median levels of all markers were significantly different between young (<65 years) and old (≥65 years) subjects (Aβ42: P = .03; tau: P = .02; p-tau: P = .002; tau/Aβ42: P = .004; p-tau/Aβ42: P = .03). The association of marker levels with age was confirmed in linear regression models, where a positive relationship with age was observed for total tau (B = 2.3; 95% confidence interval [CI]: 0.89 to 3.7; P = .002), p-tau (B = 0.5; 95% CI: 0.1 to 0.9; P = .02), and tau/Aβ42 ratio (B = 0.006; 95% CI: 0.002 to 0.01; P = .002). No subjects showed abnormal tau, whereas 19% showed abnormal CSF Aβ42 concentrations. CONCLUSION: In cognitively normal subjects, the concentrations of CSF biomarkers of AD are associated with age. Further longitudinal studies could clarify whether Aβ42 low levels represent a preclinical AD biomarker.
Authors: Jon B Toledo; Henrik Zetterberg; Argonde C van Harten; Lidia Glodzik; Pablo Martinez-Lage; Luisella Bocchio-Chiavetto; Lorena Rami; Oskar Hansson; Reisa Sperling; Sebastiaan Engelborghs; Ricardo S Osorio; Hugo Vanderstichele; Manu Vandijck; Harald Hampel; Stefan Teipl; Abhay Moghekar; Marilyn Albert; William T Hu; Jose A Monge Argilés; Ana Gorostidi; Charlotte E Teunissen; Peter P De Deyn; Bradley T Hyman; Jose L Molinuevo; Giovanni B Frisoni; Gurutz Linazasoro; Mony J de Leon; Wiesje M van der Flier; Philip Scheltens; Kaj Blennow; Leslie M Shaw; John Q Trojanowski Journal: Brain Date: 2015-07-27 Impact factor: 13.501
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Authors: Brandon E Gavett; Samantha E John; Ashita S Gurnani; Cara A Bussell; Jessica L Saurman Journal: J Alzheimers Dis Date: 2016 Impact factor: 4.472
Authors: Argonde C Van Harten; Heather J Wiste; Stephen D Weigand; Michelle M Mielke; Walter K Kremers; Udo Eichenlaub; Richard Batrla-Utermann; Roy B Dyer; Alicia Algeciras-Schimnich; David S Knopman; Clifford R Jack; Ronald C Petersen Journal: Neurology Date: 2020-06-26 Impact factor: 9.910
Authors: Lucette A Cysique; Timothy Hewitt; Juliana Croitoru-Lamoury; Kevin Taddei; Ralph N Martins; Constance S N Chew; Nicholas N W S Davies; Patricia Price; Bruce J Brew Journal: BMC Neurol Date: 2015-04-01 Impact factor: 2.474