Journal of Alzheimer's Disease - Volume 68, issue 1

Authors: Seino, Yusuke | Nakamura, Takumi | Kawarabayashi, Takeshi | Hirohata, Mie | Narita, Sakiko | Wakasaya, Yasuhito | Kaito, Kozue | Ueda, Tetsuya | Harigaya, Yasuo | Shoji, Mikio

Article Type: Research Article

Abstract: Cerebrospinal fluid (CSF) amyloid-β (Aβ)42 and tau are biomarkers for Alzheimer’s disease (AD); however, the effects of other neurodegenerative processes on these biomarkers remain unclear. We measured Aβ40 , Aβ42 , total tau, phosphorylated-tau, and α -synuclein in CSF and plasma using matched samples from various neurodegenerative diseases to expand our basic knowledge on these biomarkers and their practical applications. A total of 213 CSF and 183 plasma samples were analyzed from cognitively unimpaired subjects, and patients with Alzheimer’s disease dementia (ADD), mild cognitive impairment (MCI), non-AD dementias, and other neurological diseases. The CSF/plasma ratios of Aβ40 and …Aβ42 were approximately 25:1. Aβ40/42 ratios in CSF and plasma were both 10:1. The CSF total tau/P181tau ratio was 6:1. The CSF/plasma α -synuclein ratio was 1:65. Significantly decreased Aβ42 levels and an increased Aβ40/42 ratio in CSF in ADD/MCI suggested that these relationships were specifically altered in AD. Increased total tau levels in ADD/MCI, encephalopathy, and multiple system atrophy, and increased P181tau in ADD/MCI indicated that these biomarkers corresponded to neurodegeneration and tauopathy, respectively. Although CSF α -synuclein levels were increased in ADD/MCI, there was no merit in measuring α -synuclein in CSF or plasma as a biomarker. The combination of biomarkers by the Aβ40/42 ratio×p181tau reflected specific changes due to the AD pathology in ADD/MCI. Thus, CSF Aβ40 , Aβ42 , p181tau, and tau were identified as biomarkers for aggregated Aβ associated state (A), aggregated tau associated state (T), and neurodegeneration state (N) pathologies in AD based on the NIA-AA criteria. Overlaps in these biomarkers need to be considered in clinical practice for differential diagnoses of neurodegenerative diseases. Show more

Keywords: Aβ40, Aβ42, α-synuclein, cerebrospinal fluid, neurodegenerative diseases, phosphorylated-tau, plasma, total-tau

DOI: 10.3233/JAD-181152

Citation: Journal of Alzheimer's Disease, vol. 68, no. 1, pp. 395-404, 2019

Authors: Xia, Hui | Wang, Min | Li, Jie-Qiong | Tan, Chen-Chen | Cao, Xi-Peng | Tan, Lan | Yu, Jin-Tai | Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: The brain-derived neurotrophic factor (BDNF ) Val66Met polymorphism emerged as a risk factor for Alzheimer’s disease (AD). However, little was known about its effects on the process of potential AD. Objective: To explore the effects of the Val66Met polymorphism on cognition, cerebrospinal fluid (CSF), and neuroimaging markers in non-demented elderly individuals. Methods: A total of 1,081 adults without dementia (375 healthy subjects and 706 individuals with mild cognitive impairment) were recruited from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to test the influence of BDNF Val66Met polymorphism on cognitive impairment, brain structure atrophy, and change …in the levels of CSF biomarkers. Moreover, we also conducted our study in abnormal amyloid-β (A +) subgroup and normal amyloid-β (A–) subgroup, as well as in APOE ɛ 4 carriers and non-carriers. Results: The BDNF Val66Met polymorphism had significant association with atrophy of the entorhinal cortex and Mini-Mental State Examination (MMSE) scores in the non-demented elderly and A  + subgroup, while no association was found in A–subgroup. What is more, there was a significant effect of interaction between BDNF Val66Met and amyloid-β load in MMSE. In addition, significant associations of BDNF Val66Met with the entorhinal cortex and ventricular volumes were found among APOE ɛ 4 non-carriers, but not APOE ɛ 4 carriers. Conclusions: The BDNF Val66Met polymorphism is associated with cognitive impairment and brain atrophy among the non-demented elderly, APOE ɛ 4 non-carriers and A  + subgroup, implying the potential of the Val66Met polymorphism as an important genetic factor for AD-related neurodegeneration. Show more

Keywords: Alzheimer’s disease, amyloid-β, brain-derived neurotrophic factor, polymorphism

DOI: 10.3233/JAD-180971

Citation: Journal of Alzheimer's Disease, vol. 68, no. 1, pp. 405-414, 2019

Authors: Gulisano, Walter | Maugeri, Daniele | Baltrons, Marian A. | Fà, Mauro | Amato, Arianna | Palmeri, Agostino | D’Adamio, Luciano | Grassi, Claudio | Devanand, D.P. | Honig, Lawrence S. | Puzzo, Daniela | Arancio, Ottavio

Article Type: Correction

DOI: 10.3233/JAD-189015

Citation: Journal of Alzheimer's Disease, vol. 68, no. 1, pp. 415-415, 2019