Neuropathological investigation of hypocretin expression in brains of dementia with Lewy bodies.
Hypocretin (Hcrt) is a neuropeptide synthesized in the lateral hypothalamus (LHT) that plays a key role in maintaining arousal state. In Parkinson's disease (PD), a narcolepsy-like syndrome is commonly seen, and a previous study showed substantial Hcrt neuronal loss in accordance with PD severity. In the present study, we quantitatively examined Hcrt immunoreactivity and α-synuclein and tau pathologies in the LHT and locus coeruleus (LC) in dementia with Lewy bodies (DLB) (n=15), Alzheimer's disease (AD) (n=14), and controls (n=7). In the LHT, substantial Hcrt-positive neurons were detected in controls. In contrast, in DLB and AD, the numbers of both total neurons and Hcrt-positive neurons were significantly reduced. The reduction of the latter was significantly severer in DLB than in AD. In the LC of controls, many Hcrt-positive axonal terminals were found. In contrast, the amount of Hcrt immunoreactivity was significantly reduced both in DLB and AD. In DLB, some Lewy body (LB)-bearing neurons were detected in the LHT, but the Hcrt-positive neurons did not have any LBs. Meanwhile, some tau-positive neurofibrillary tangle (NFT)-bearing neurons were detected in the LHT, and Hcrt-positive neurons occasionally contained NFTs. We observed a significant negative correlation between the number of Hcrt-positive neurons in the LHT and the neurofibrillary stage (r=-0.67, p=0.0067), whereas no significant correlation was found between the number of Hcrt-positive neurons and the Lewy stage (r=-0.47, p=0.077). This is the first report clarifying the substantial loss of Hcrt neurons in the LHT and of Hcrt axonal terminals in the LC in DLB and the correlation between the severity of Hcrt neuronal loss and progression of neurofibrillary pathology.
PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Juntendo University School of Medicine, 3-3-20 Shinsuna, Koto-ku, Tokyo 136-0075, Japan; Department of Psychiatry, Juntendo University School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: ksnk1jobim@yahoo.co.jp.
Koji
K
Kasanuki
PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Juntendo University School of Medicine, 3-3-20 Shinsuna, Koto-ku, Tokyo 136-0075, Japan; Department of Psychiatry, Juntendo University School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Eizo
E
Iseki
PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Juntendo University School of Medicine, 3-3-20 Shinsuna, Koto-ku, Tokyo 136-0075, Japan; Department of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Daizo
D
Kondo
PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Juntendo University School of Medicine, 3-3-20 Shinsuna, Koto-ku, Tokyo 136-0075, Japan.
Hiroshige
H
Fujishiro
PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Juntendo University School of Medicine, 3-3-20 Shinsuna, Koto-ku, Tokyo 136-0075, Japan.
Michiko
M
Minegishi
PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Juntendo University School of Medicine, 3-3-20 Shinsuna, Koto-ku, Tokyo 136-0075, Japan.
Kiyoshi
K
Sato
Department of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Omi
O
Katsuse
Department of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Hiroaki
H
Hino
Department of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Kenji
K
Kosaka
Department of Psychiatry, Juntendo University School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Heii
H
Arai
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D020961:Lewy Body Disease / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D000068797:Orexins; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D051844:alpha-Synuclein; D016875:tau Proteins
Dementia with Lewy bodies; Hypocretin; Narcolepsy; Neuropathology; Tau; α-Synuclein