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Cerebrospinal Fluid Tau and Amyloid β Proteins Do Not Correlate With Cognitive Functioning in Cognitively Impaired Memory Clinic Patients

Published online by Cambridge University Press:  07 November 2014

Abstract

Objective: The aim of this study was to investigate the influence of cerebrospinal fluid (CSF), amyloid β42(Aβ42), phosphorylated tau181 (p-tau), and total tau (t-tau) on cognitive functioning.

Methods: We analyzed the ability of the CSF biomarkers Aβ42, p-tau, and t-tau to predict the results on the Cambridge Cognitive Examination–Revised (CAMCOG-R), a cognitive screening test that assesses multiple cognitive domains, in 65 memory clinic patients (73.1±8.2 years) (n=30 probable Alzheimer's disease [AD], n=7 possible AD, n=12 non-AD dementia, n=16 mild cognitive impairment).

Results: We found no correlations between CSF biomarkers and CAMCOG-R performance in the whole group, nor in subgroups based on aberrant biomarker concentrations.

Discussion: Changed concentrations of CSF amyloid β42, p-tau, and t-tau cannot be directly linked to cognitive function in our sample of patients with cognitive impairment. Possibly, compensatory mechanisms such as cognitive reserve determine cognitive performance, rather than the absolute amount of damage caused by Aβ deposition and tangle formation. In addition, abnormal CSF biomarker concentrations may not be a direct reflection of the amount of neuronal damage, but merely serve as an indicator of AD pathology.

Conclusion: While CSF biomarkers are valuable in establishing AD pathology, they cannot be used to predict severity of cognitive impairment.

Type
Original Research
Copyright
Copyright © Cambridge University Press 2010

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References

REFERENCES

1.Blennow, K. CSF biomarkers for mild cognitive impairment. J Intern Med. 2004; 256(3): 224234.CrossRefGoogle ScholarPubMed
2.de Jong, D, Kremer, BP, Olde Rikkert, MG, et al. Current state and future directions of neurochemical biomarkers for Alzheimer's disease. Clin Chem Lab Med. 2007; 45(11): 14211434.CrossRefGoogle ScholarPubMed
3.Visser, PJ, Verhey, F, Knol, DL, et al. Prevalence and prognostic value of CSF markers of Alzheimer's disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study. Lancet Neurol. 2009; 8(7): 619627.CrossRefGoogle ScholarPubMed
4.Suh, YH, Checler, F. Amyloid precursor protein, presenilins, and alpha-synuclein: molecular pathogenesis and pharmacological applications in Alzheimer's disease. Pharmacol Rev. 2002; 54(3): 469525.CrossRefGoogle ScholarPubMed
5.Jack, CR Jr, Knopman, DS, Jagust, WJ, et al. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 2010; 9(1): 119128.CrossRefGoogle ScholarPubMed
6.Engelborghs, S, Maertens, K, Vloeberghs, E, et al. Neuropsychological and behavioural correlates of CSF biomarkers in dementia. Neurochem Int. 2006; 48(4): 286295.CrossRefGoogle ScholarPubMed
7.Ivanoiu, A, Sindic, CJ. Cerebrospinal fluid TAU protein and amyloid beta42 in mild cognitive impairment: prediction of progression to Alzheimer's disease and correlation with the neuropsychological examination. Neurocase. 2005; 11(1): 3239.CrossRefGoogle ScholarPubMed
8.Riemenschneider, M, Schmolke, M, Lautenschlager, N, et al. Association of CSF apolipoprotein E, Abeta42 and cognition in Alzheimer's disease. Neurobiol Aging. 2002; 23(2): 205211.CrossRefGoogle ScholarPubMed
9.Sunderland, T, Linker, G, Mirza, N, et al. Decreased beta-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease. JAMA. 2003; 289(16): 20942103.CrossRefGoogle ScholarPubMed
10.Olin, JT, Zelinski, EM. The 12-month reliability of the Mini-Mental State Examination. Psychol Assessment. 1991; 3(3): 427432.CrossRefGoogle Scholar
11.Schmand, B, Lindeboom, J, Hooijer, C, et al. Relation between education and dementia: the role of test bias revisited. J Neurol Neurosurg Psychiatry. 1995; 59(2): 170174.CrossRefGoogle ScholarPubMed
12.van der Vlies, AE, Verwey, NA, Bouwman, FH, et al. CSF biomarkers in relationship to cognitive profiles in Alzheimer disease. Neurology. 2009; 72(12): 10561061.CrossRefGoogle ScholarPubMed
13.Tsolaki, M, Sakka, V, Gerasimou, G, et al. Correlation of rCBF (SPECT), CSF tau, and cognitive function in patients with dementia of the Alzheimer's type, other types of dementia, and control subjects. Am J Alzheimers Dis Other Demen. 2001; 16(1): 2131.CrossRefGoogle ScholarPubMed
14.Hildebrandt, H, Haldenwanger, A, Eling, P. False recognition correlates with amyloid-beta (1-42) but not with total tau in cerebrospinal fluid of patients with dementia and mild cognitive impairment. J Alzheimers Dis. 2009; 16(1): 157165.CrossRefGoogle Scholar
15.Roth, M, Huppert, FA, Mountjoy, CQ, et al. The Revised Cambridge Examination for Mental Disorders of the Elderly. Cambridge University Press. 1999.Google Scholar
16.Schmand, B, Walstra, G, Lindeboom, J, et al. Early detection of Alzheimer's disease using the Cambridge Cognitive Examination (CAMCOG). Psychol Med. 2000; 30(3): 619627.CrossRefGoogle ScholarPubMed
17.McKhann, G, Drachman, D, Folstein, M, et al. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984; 34(7): 939944.CrossRefGoogle ScholarPubMed
18.Winblad, B, Palmer, K, Kivipelto, M, et al. Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med. 2004; 256(3): 240246.CrossRefGoogle Scholar
19.Savva, GM, Wharton, SB, Ince, PG, et al. Age, neuropathology, and dementia. N Engl J Med. 2009; 360(22): 23022309.CrossRefGoogle ScholarPubMed
20.Gandy, S. The role of cerebral amyloid beta accumulation in common forms of Alzheimer disease. J Clin Invest. 2005; 115(5): 11211129.Google ScholarPubMed
21.Schmand, B, Huizenga, HM, van Gool, WA. Meta-analysis of CSF and MRI biomarkers for detecting preclinical Alzheimer's disease. Psychol Med. 2010; 40(1): 135145.CrossRefGoogle ScholarPubMed
22.Andreasen, N, Hesse, C, Davidsson, P, et al. Cerebrospinal fluid beta-amyloid(1-42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease. Arch Neurol. 1999; 56(6): 673680.CrossRefGoogle ScholarPubMed
23.Sluimer, JD, Bouwman, FH, Vrenken, H, et al. Whole-brain atrophy rate and CSF biomarker levels in MCI and AD: A longitudinal study. Neurobiol Aging. 2008;Google Scholar
24.Zetterberg, H, Pedersen, M, Lind, K, et al. Intra-individual stability of CSF biomarkers for Alzheimer's disease over two years. J Alzheimers Dis. 2007; 12(3): 255260.CrossRefGoogle ScholarPubMed
25.Strozyk, D, Blennow, K, White, LR, et al. CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology. 2003; 60(4): 652656.CrossRefGoogle Scholar
26.Engelborghs, S, Sleegers, K, Cras, P, et al. No association of CSF biomarkers with APOEepsilon4, plaque and tangle burden in definite Alzheimer's disease. Brain. 2007; 130(Pt 9): 23202326.CrossRefGoogle ScholarPubMed
27.Ingelsson, M, Fukumoto, H, Newell, KL, et al. Early Abeta accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain. Neurology. 2004; 62(6): 925931.CrossRefGoogle ScholarPubMed