Tail Proteins in Cerebrospinal Fluid from Patients with Alzheimer's Disease: A Longitudinal Study

Isoe, Kenji; Urakami, Katsuya; Shimomura, Tokio; Wakutani, Yosuke; Ji, Yong Sok; Adachi, Yoshiki; Takahashi, Kentaro

doi:10.1159/000106874

Cited by 14 publications

(8 citation statements)

References 3 publications

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“…Studies investigating the correlation between degree of dementia and CSF tau are contradictory too; most studies could not demonstrate such a correlation [9,10,21,28]. Others have reported a significant elevation of tau with increasing functional assessment staging scores [14,29]. These conflicting results might be due to differences in age and degree of dementia in the studied groups, since some results indicate that the relation between CSF tau and clinical progression of AD does not fit into linear regression models but rather increases in early stages and declines in severe AD [10,11,22,29].…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Tau Levels Increase with Age in Healthy Individuals

Blomberg

Jensen²,

Basun³

et al. 2001

Dement Geriatr Cogn Disord

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Cerebrospinal fluid (CSF) tau is a promising biochemical ante-mortem marker for Alzheimer’s disease (AD). Levels are increased in AD compared to other dementias, neurological diseases and healthy controls. An age-related decrease in both soluble tau and tau bound to paired helical filaments has been shown in brains from non-demented subjects. To study tau levels in normal ageing, we investigated CSF in 29 healthy individuals aged 45–80 years. A statistically significant increase in CSF tau with increasing age was found which might be caused by neuronal loss during normal ageing and redistribution of soluble tau from the brain into CSF. We could not demonstrate any influence by the APOE genotype, though larger populations have to be investigated to confirm this result. In conclusion, we found an age-dependent increase in CSF tau in healthy individuals. We emphasise the importance of establishing an age-dependent interval of CSF tau in non-demented subjects.

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Tau Levels Increase with Age in Healthy Individuals

Blomberg

Jensen²,

Basun³

et al. 2001

Dement Geriatr Cogn Disord

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“…Recent studies of biomarkers have specifically focused on the analysis of cerebrospinal fluid (CSF) levels of microtubule‐associated protein tau and amyloid β‐protein ending at amino acid 42 (Aβ42). By using a sensitive enzyme‐linked immunosorbent assay (ELISA), several independent groups have confirmed that tau levels are increased4–6 and Aβ42 levels are decreased7, 8 in CSF samples from patients with AD compared to normal controls and patients with certain neurological diseases. The most widely used ELISA for tau employs antibodies that are independent of the phosphorylation state of tau 9.…”

mentioning

confidence: 99%

Large‐scale, multicenter study of cerebrospinal fluid tau protein phosphorylated at serine 199 for the antemortem diagnosis of Alzheimer's disease

Itoh

Arai

Urakami

et al. 2001

Annals of Neurology

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We surveyed a total of 570 cerebrospinal fluid (CSF) samples from a variety of diseases, including Alzheimer's disease (AD; n = 236), non-AD-demented and nondemented diseases (n = 239), and normal controls (n = 95) to quantitate levels of tau protein phosphorylated at serine 199 (CSF/phospho-tau199) by a recently established sandwich ELISA. The CSF/phospho-tau199 levels in the AD group were significantly elevated compared to those in all the other non-AD groups. Receiver operating characteristics curves showed that the diagnostic sensitivity and specificity for the AD group vs all the other non-AD groups using the CSF/phospho-tau199 were 85.2% and 85.0%, respectively. Furthermore, there was a significant positive correlation between CSF/phospho-tau199 and CSF/total-tau levels in the AD group. Elevated CSF/phospho-tau199 in the AD group was noted irrespective of age, gender, dementia severity, and number of apolipoprotein E4 alleles. Thus, we suggest that CSF/phospho-tau199 may be a novel and logical biomarker in supporting antemortem diagnosis of AD.

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“…Contradictory results concerning longitudinal changes of tau and P-tau CSF have been reported (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). In only two longitudinal studies, intra-and an inter-assay variability are mentioned (6,8), and not more than three studies explicitly reported that baseline and follow-up CSF samples were assayed in the same analytical run (9,17,18).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies described longitudinal changes of tau and P-tau level in CSF and showed contradictory results (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). These contradictory results are probably not only due to the biological variability in the CSF samples but also to effects of CSF processing, complicating studies measuring longitudinal changes in these biomarkers (19).…”

Section: Introductionmentioning

confidence: 99%