Increasing cerebrospinal fluid tau levels in a subgroup of Alzheimer patients with apolipoprotein E allele ϵ4 during 14 months follow-up

doi:10.1016/0304-3940(96)12905-0

Neuroscience Letters

Volume 214, Issues 2–3, 23 August 1996, Pages 163-166

https://doi.org/10.1016/0304-3940(96)12905-0 Get rights and content

Abstract

The concentration of tau protein is elevated in the cerebrospinal fluid (CSF) in Alzheimer's disease (AD), suggesting that CSF tau may be a useful biochemical diagnostic marker for this disorder. We investigated CSF tau concentrations on two occassions in AD (n = 18), mild cognitive impairment (MCI, n = 9) and other dementing diseases (OD, n = 9) by ELISA (Innotest hTau Antigen®, Innogenetics, Belgium). Tau levels were statistically significant higher in the AD group than in MCI and OD groups on both occasions. Twelve of the AD patients showed increasing values of tau at follow-up and six demonstrated diminished values. All AD patients with increasing tau were carriers of one or two ϵ4 alleles of the apolipoprotein E (APOE) gene. Of those AD cases with decreasing tau levels only three individuals had the ϵ4 allele, a difference that was statistically significant (P < 0.05). These findings suggest that there may be apolipoprotein E (apoE) isoform-specific differences of tau regulation in AD.

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Cerebrospinal fluid (CSF) samples are commonly collected via lumbar puncture (LP) in both clinical and research settings for measurement of biomarkers of Alzheimer’s disease (AD). To determine the effects of LP on CSF AD biomarkers, we collected CSF samples at seven different time points after an LP in rhesus monkeys. We find that amyloid-beta (Aβ) and Tau levels increased significantly on day 1, peaked on day 3, and returned to baseline on day 10 after LP. The NFL levels increased significantly on day 5, peaked on day 10, and returned to baseline after day 30. The increased AD biomarker levels were mainly due to CSF outflow and deep intrathecal invasion during LP. Therefore, if LPs are repeated within a short period of time, prior LP can affect Aβ and Tau levels within 10 days and NFL levels within 30 days, which may lead to clinical misdiagnosis or incorrect scientific conclusions.
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Citation Excerpt :
The finding of positive association between age and T-tau is in agreement with other previously published data (Blomberg et al., 2001; Briani et al., 2002; Itoh et al., 2001; Shoji et al., 1998; Sjogren et al., 2001). However, there are also contrary findings (Andreasen et al., 1998; Blomberg et al., 1996; Burkhard et al., 2004; Jensen et al., 1995; Lewczuk et al., 2004a,b). However, in some of the published negative reports, the samples were much smaller than in our study.
While cerebrospinal fluid (CSF) biomarkers are of use in the prediction and diagnosis of Alzheimer's disease our understanding of the background effects of age and the ApoE genotype is limited. Seventy-eight community-based normal volunteers (mean age 60 ± 10 years, range 36–86) were examined to determine the relationships between CSF measures of total tau (T-tau), hyperphosphorylated tau (P-tau 231), amyloid beta (Aβ42/Aβ40 ratio), and isoprostane (IP) with age and ApoE genotype. The results showed that age by ɛ4 genotype interactions were found for P-tau231 (β = 1.82; p < 0.05) and IP (β = 1.6; p < 0.05). T-tau CSF concentration increased with age. The increasing CSF concentrations of P-tau and IP in ɛ4 carriers suggest that early tauopathy and oxidative stress may be related to the increased risk for AD. The data also suggest that T-tau changes are more age dependent than Aβ changes. The evidence that P-tau231 and IP are the earliest markers for the neuronal damage related to AD awaits longitudinal study.
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Forty memory clinic patients (47.5% females), aged 61.3 ± 7.6 (S.D.) years, non-demented at baseline, underwent lumbar puncture and neuropsychological testing at two occasions. Baseline mean MMSE-score was 28.3 ± 1.8. Patients were divided into three groups based on baseline memory functioning; severely impaired (SIM), moderately impaired (MIM) and no impairment (NIM).
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Increasing cerebrospinal fluid tau levels in a subgroup of Alzheimer patients with apolipoprotein E allele ϵ4 during 14 months follow-up

Abstract

J. Psychiat. Res.

Trends. Neurol. Sci.

Neurosci. Lett.

Tau in cerebrospinal fluid: a potential diagnostic marker in Alzheimer's disease

Ann. Neurol.

APOE polymorphism is not a risk factor for cognitive impairment and haemorrhagic stroke from age 75 onwards

Stroke

A new clinical scale for the staging of dementia

Br. J. Psychiatry

A 68: a major subunit of paired helical filaments and derivatized forms of normal tau

Science

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