Cerebrospinal Fluid Biomarkers for Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex

Objective. Amyotrophic lateral sclerosis/parkinsonism-dementia complex is classified as one of the tauopathies. Methods. The total tau, phosphorylated tau, and amyloid β42 levels were assayed in cerebrospinal fluid from patients with Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex ( ), Alzheimer’s disease ( ), Parkinson’s disease ( ), amyotrophic lateral sclerosis ( ), and controls ( ) using specific enzyme-linked immunosorbent assay methods. Results. Total tau and phosphorylated tau did not increase and amyloid β42 was relatively reduced in Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex. Relatively reduced amyloid β42 might discriminate Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex from amyotrophic lateral sclerosis and Parkinson’s disease, and the ratios of phosphorylated-tau to amyloid β42 could discriminate Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex from Alzheimer’s disease. Conclusions. Cerebrospinal fluid analysis may be useful to differentiate amyotrophic lateral sclerosis/parkinsonism-dementia complex from Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease. 1. Introduction Amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a rare disorder endemic to Guam Island and the Kii Peninsula of Japan. It shows a unique combination of parkinsonism, amyotrophy, and dementia [1], and the form of dementia, which shows a phenotype similar to Alzheimer’s disease (AD), is becoming predominant in the Kii Peninsula. Although Kii ALS/PDC shows several unique clinical features, including severe atrophy of the frontal and temporal lobes on magnetic resonance imaging (MRI), decreased cerebral blood flow in the frontal and temporal lobes on single-photon emission computed tomography (SPECT) [2], pigmentary retinopathy [3], and decreased cardiac 123I-meta-iodobenzylguanidine uptake [4], a postmortem examination is required for a definitive diagnosis. Since biomarkers for ALS/PDC have not yet been identified, we analyzed cerebrospinal fluid (CSF) biomarkers for Kii ALS/PDC to discriminate it from other neurodegenerative disorders. 2. Material and Methods We collected CSF samples from 12 patients with Kii ALS/PDC (6 men, 6 women, mean age years, mean illness duration 5.63 years), nine patients with AD (2 men, 7 women, mean age years, mean illness duration 1.92 years), 11 patients with ALS (8 men, 3 women, mean age years, mean illness duration 1.1 years), nine patients with Parkinson’s disease (PD; 7 men, 2 women, mean age years, mean illness duration