CSF levels of Aβ1-38/Aβ1-40/Aβ1-42 and (11)C PiB-PET studies in three clinical variants of primary progressive aphasia and Alzheimer's disease.

Abstract

Primary progressive aphasia (PPA) is a cognitive syndrome characterized by progressive and isolated language impairments due to neurodegenerative diseases. Recently, an international group of experts published a Consensus Classification of the three PPA clinical variants (naPPA, svPPA and lvPPA). We analyzed 24 patients with PPA by cognitive functions, neuroimaging (MRI, (99 m)Tc ECD-SPECT, (11)C PiB-PET and FDG-PET) and cerebrospinal fluid (CSF) analysis (ptau-181, Aβ1-42, Aβ1-40 and Aβ1-38), to elucidate relationships between neuroimaging studies and biochemical findings in the three PPA clinical variants. Cognitive and speech functions were measured by mini-mental state examination and standard language test of aphasia. The patients with lvPPA showed significant decreases in CSF Aβ1-42 and ratios of Aβ1-42/Aβ1-40 and Aβ1-42/Aβ1-38, and significant increases in CSF ptau-181 and ratios of ptau-181/Aβ1-42 and ptau-181/Aβ1-38; these findings were similar to those of patients with Alzheimer's disease (AD). We observed a higher frequency of the ApoE ε4 allele in the lvPPA patients relative to the two other PPA variants. In (11)C PiB-PET of lvPPA patients, PiB positive findings were detected in cortices of frontal, temporal and parietal lobes and the posterior cingulate, where massive Aβ may accumulate due to AD. Our results of AD-CSF markers including Aβ1-38 and (11)C PiB-PET in the lvPPA patients demonstrate a common pathological mechanism with the occurrence of AD.

• Authors: Masaki Ikeda, Yuichi Tashiro, Eriko Takai, Sachiko Kurose, Naoko Fugami, Kazuhisa Tsuda, Yukiko Arisaka, Sayaka Kodaira, Yukio Fujita, Kouki Makioka, Yuji Mizuno, Hirotaka Shimada, Yasuo Harigaya, Masamitsu Takatama, Masakuni Amari, Tsuneo Yamazaki, Haruyasu Yamaguchi, Tetsuya Higuchi, Koichi Okamoto, Yoshito Tsushima, Yoshio Ikeda
• Journal: Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis (Amyloid) Vol. 21 Issue 4 Pg. 238-45 (Dec 2014) ISSN: 1744-2818 [Electronic] England
• PMID: 25139672 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Apolipoproteins E
• Biomarkers

Topics

• Alzheimer Disease (cerebrospinal fluid, diagnostic imaging, genetics)
• Amyloid beta-Peptides (cerebrospinal fluid)
• Aphasia, Primary Progressive (cerebrospinal fluid, diagnostic imaging, genetics)
• Apolipoproteins E (genetics)
• Biomarkers (cerebrospinal fluid)
• Humans
• Language Tests
• Positron-Emission Tomography