Homovanillic acid and 5-hydroxyindole acetic acid as biomarkers for dementia with Lewy bodies and coincident Alzheimer's disease: An autopsy-confirmed study.
Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are the two most common causes of dementia. Both pathologies often coexist, and AD patients with concomitant neocortical LB pathology (referred to as the Lewy body variant of AD) generally show faster cognitive decline and accelerated mortality relative to patients with pure AD. Thus, discriminating among patients with DLB, AD, and coincident DLB and AD is important in clinical practice. We examined levels of homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), tau, phosphorylated tau (p-tau), and beta-amyloid (Aβ) 1-42 in cerebrospinal fluid (CSF) to evaluate their viability as biomarkers to discriminate among different forms of dementia. We obtained a total of 3498 CSF samples from patients admitted to our hospital during the period from 1996 to 2015. Of these patients, we were able to carry out a brain autopsy in 94 cases. Finally, 78 neuropathologically diagnosed cases (10 AD, six DLB, five DLB with AD, five controls without neurological diseases, and 52 cases with other neurological diseases) were studied. CSF levels of HVA and 5-HIAA were consistently decreased in pathologically advanced Lewy body disorder (LBD; Braak LB stages >3) compared with pathologically incipient LBD (Braak LB stages <2). These results suggest that if an individual has LB pathology in the central nervous system, CSF levels of HVA and 5-HIAA may decrease after the onset of clinical symptoms. In addition, CSF levels of HVA and 5-HIAA decreased with LB pathology, and were especially low in cases of DLB and DLB with AD. Furthermore, the combination of HVA, 5-HIAA, and brain specific proteins t-tau, p-tau, and Aβ 1-42 in CSF were useful for discriminating among DLB, DLB with AD, and AD with high diagnostic accuracy.
Department of Neuropathology, Tokyo Metropolitan Geriatric Hospital and Institution of Gerontology, Tokyo, Japan.|Department of Neurology, Tokyo Metropolitan Geriatric Hospital and Institution of Gerontology, Tokyo, Japan.
Satoru
http://orcid.org/0000-0003-0022-9529
S
Morimoto
Department of Neuropathology, Tokyo Metropolitan Geriatric Hospital and Institution of Gerontology, Tokyo, Japan.|Department of Neurology and Stroke, Saitama Medical University International Medical Center, Saitama, Japan.
Masaki
M
Takao
Department of Neuropathology, Tokyo Metropolitan Geriatric Hospital and Institution of Gerontology, Tokyo, Japan.
Hiroyuki
H
Hatsuta
Department of Neurology, Tokyo Metropolitan Geriatric Hospital and Institution of Gerontology, Tokyo, Japan.
Yasushi
Y
Nishina
Department of Neurology, National Hospital Organization Tokyo National Hospital, Tokyo, Japan.
Tadashi
T
Komiya
Department of Neurology, Tokyo Metropolitan Geriatric Hospital and Institution of Gerontology, Tokyo, Japan.
Renpei
R
Sengoku
Department of Neuropathology, Tokyo Metropolitan Geriatric Hospital and Institution of Gerontology, Tokyo, Japan.
Yuta
Y
Nakano
Department of Neuropathology, Tokyo Metropolitan Geriatric Hospital and Institution of Gerontology, Tokyo, Japan.
Akiko
A
Uchino
Department of Neuropathology, Tokyo Metropolitan Geriatric Hospital and Institution of Gerontology, Tokyo, Japan.
Hiroyuki
H
Sumikura
Department of Laboratory Medicine, National Center of Neurology and Psychiatry, Tokyo, Japan.
Yuko
Y
Saito
Department of Neurology, Tokyo Metropolitan Geriatric Hospital and Institution of Gerontology, Tokyo, Japan.
Kazutomi
K
Kanemaru
Department of Neuropathology, Tokyo Metropolitan Geriatric Hospital and Institution of Gerontology, Tokyo, Japan.|Department of Neurology, Tokyo Metropolitan Geriatric Hospital and Institution of Gerontology, Tokyo, Japan.
Shigeo
S
Murayama
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000150:complications* / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001344:Autopsy; D015415:Biomarkers; D003937:Diagnosis, Differential; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid*; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid* / Q000150:complications* / Q000175:diagnosis; D008875:Middle Aged; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid