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P1‐254: NON‐ALZHEIMER'S DISEASE SUBJECTS OCCASIONALLY MIMIC CSF PATTERN OF PRECLINICAL ALZHEIMER'S DISEASE
Author(s) -
Kasuga Kensaku,
Tsukie Tamao,
Tokutake Takayoshi,
Miura Takeshi,
Mezaki Naomi,
Ishiguro Takanobu,
Miyashita Akinori,
Onodera Osamu,
Ikeuchi Takeshi
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.260
Subject(s) - clusterin , cerebrospinal fluid , biomarker , medicine , pathology , tau protein , alzheimer's disease , disease , oncology , chemistry , apoptosis , biochemistry
Background:It has been shown that cerebrospinal fluid (CSF) b-amyloid1-42 (Ab1-42) levels show an inverse correlation with brain amyloid plaques, whereas total tau (t-tau) and phosphorylated tau (ptau) levels correlate with the number of neurofibrillary tangles in the brain. Accordingly, reduced CSF Ab1-42 is a useful biomarker for detecting Alzheimer’s disease (AD) subjects even in the preclinical stage. However, reduction of CSFAb1-42 has also been reported in non-AD subjects. To determine a characteristic CSF pattern of non-AD subjects with reduced CSF Ab1-42, we classified subjects with various neurological disorders into four categories based on levels of CSF Ab1-42 and p-tau, then investigated additional CSF biomarkers in each category. Methods: A total of 182 subjects were included in this study. We measured Ab1-42, t-tau, p-tau in CSF using xMap technology, subsequently classified subjects into four categories independently of clinical diagnosis: non-low Ab142/non-high p-tau (n1⁄449), non-low Ab1-42/high p-tau (n1⁄426), low Ab1-42/non-high p-tau (n1⁄458), and low Ab1-42/high p-tau (socalled AD signature, n1⁄449). Next, levels of Ab1-38 and Ab1-40 were measured by MSD, and levels of apoE and Clusterin (apoJ) were measured by ELISA kits. Each biomarker level of four categories was compared, and correlation between each biomarker was analyzed. Results:As expected, more than half subjects categorized as AD signature were clinically diagnosed as AD. Interestingly, a group categorized as low Ab1-42/non-high p-tau included many subjects with progressive supranuclear palsy and idiopathic normal pressure hydrocephalus. Subjects categorized as AD signature showed the reduction of only Ab1-42 level, but not Ab1-38 and Ab1-40. In contrast, in a group categorized as low Ab1-42/non-high p-tau, levels of all Ab species were significantly reduced compared to other groups. Furthermore, this group showed the lowest level of t-tau. Levels of apoE were significantly correlated with all Ab species, whereas levels of Clusterin (apoJ) were correlated well with only Ab1-38 and Ab1-40. Conclusions:There is a group of subjects who show reduced CSFAb1-42 mimicking preclinical AD although they are not expected to have Alzheimer’s pathology in the brain. Their feature is reduced levels of Ab1-38, Ab1-40 and t-tau in CSF.

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