CSF P-Tau181 and Other Biomarkers in Patients With Neuronal Intranuclear Inclusion Disease

被引：16

作者：

Kurihara, Masanori ^{[1
,2
]}

Komatsu, Hiroki ^{[1
,2
]}

Sengoku, Renpei ^{[1
,2
,3
,4
,5
]}

Shibukawa, Mari ^{[1
,2
,6
]}

Morimoto, Satoru ^{[1
,2
,7
]}

Matsubara, Tomoyasu ^{[1
,2
,3
,4
]}

Arakawa, Akira ^{[1
,2
,3
,4
]}

Orita, Makoto ^{[3
,4
]}

Ishibashi, Kenji ^{[8
]}

Mitsutake, Akihiko ^{[9
]}

Shibata, Shota ^{[9
]}

Ishiura, Hiroyuki ^{[9
]}

Adachi, Kaori ^{[10
]}

Ohse, Kensuke ^{[11
]}

Hatano, Keiko ^{[1
,2
]}

Ihara, Ryoko ^{[1
,2
]}

Higashihara, Mana ^{[1
,2
]}

Nishina, Yasushi ^{[1
,2
]}

Tokumaru, Aya Midori ^{[12
,13
]}

Ishii, Kenji ^{[8
]}

Saito, Yuko ^{[3
,4
]}

Murayama, Shigeo ^{[1
,2
,3
,4
,14
,15
]}

Kanemaru, Kazutomi ^{[1
,2
]}

Iwata, Atsushi ^{[1
,2
,11
]}

机构：

[1] Jikei Univ, Tokyo Metropolitan Geriatric Hosp, Sch Med, Dept Neurol, Tokyo, Japan

[2] Jikei Univ, Inst Gerontol, Sch Med, Tokyo, Japan

[3] Jikei Univ, Tokyo Metropolitan Geriatr Hosp, Sch Med, Dept Neuropathol Brain Bank Aging Res, Tokyo, Japan

[4] Jikei Univ, Sch Med, Inst Gerontol, Tokyo, Japan

[5] Jikei Univ, Sch Med, Dept Neurol, Tokyo, Japan

[6] Toho Univ, Fac Med, Dept Neurol, Tokyo, Japan

[7] Keio Univ, Sch Med, Dept Physiol, Tokyo, Japan

[8] Tokyo Metropolitan Inst Gerontol, Res Team Neuroimaging, Tokyo, Japan

[9] Univ Tokyo, Grad Sch Med, Dept Neurol, Tokyo, Japan

[10] Tottori Univ, Res Initiat Ctr, Org Res Initiat & Promot, Yonago, Japan

[11] Tokyo Metropolitan Geriatr Hosp, Integrated Res Initiat Living Well Dementia, Tokyo, Japan

[12] Tokyo Metropolitan Geriatr Hosp, Inst Gerontol, Tokyo, Japan

[13] Tokyo Metropolitan Geriatr Hosp, Dept Diagnost Radiol, Tokyo, Japan

[14] Osaka Univ, Inst Gerontol, Osaka, Osaka, Japan

[15] Osaka Univ, United Grad Sch Child Dev, Brain Bank Neurodev Neurol & Psychiat Disorders, Osaka, Osaka, Japan

来源：

NEUROLOGY | 2023年 / 100卷 / 10期

关键词：

HUMAN CEREBROSPINAL-FLUID; PHOSPHORYLATED TAU; ALZHEIMERS-DISEASE; BODY DISEASE; LEWY BODIES; DIAGNOSIS; PROTEIN; DEMENTIA; DEGENERATION; PATHOLOGY;

D O I：

10.1212/WNL.0000000000201647

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background and ObjectivesCSF tau phosphorylated at threonine 181 (p-tau181) is a widely used biomarker for Alzheimer disease (AD) and has recently been regarded to reflect beta-amyloid and/or p-tau deposition in the AD brain. Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease characterized by intranuclear inclusions in neurons, glial cells, and other somatic cells. Symptoms include dementia, neuropathy, and others. CSF biomarkers were not reported. The objective of this study was to investigate whether CSF biomarkers including p-tau181 are altered in patients with NIID.MethodsThis was a retrospective observational study. CSF concentrations of p-tau181, total tau, amyloid-beta 1-42 (A beta 42), monoamine metabolites homovanillic acid (HVA), and 5-hydroxyindole acetic acid (5-HIAA) were compared between 12 patients with NIID, 120 patients with Alzheimer clinical syndrome biologically confirmed based on CSF biomarker profiles, and patients clinically diagnosed with other neurocognitive disorders (dementia with Lewy bodies [DLB], 24; frontotemporal dementia [FTD], 13; progressive supranuclear palsy [PSP], 21; and corticobasal syndrome [CBS], 13). Amyloid PET using Pittsburgh compound B (PiB) was performed in 6 patients with NIID.ResultsThe mean age of patients with NIID, AD, DLB, FTD, PSP, and CBS was 71.3, 74.6, 76.8, 70.2, 75.5, and 71.9 years, respectively. CSF p-tau181 was significantly higher in NIID (72.7 +/- 24.8 pg/mL) compared with DLB, PSP, and CBS and was comparable between NIID and AD. CSF p-tau181 was above the cutoff value (50.0 pg/mL) in 11 of 12 patients with NIID (91.7%). Within these patients, only 2 patients showed decreased CSF A beta 42, and these patients showed negative or mild local accumulation in PiB PET, respectively. PiB PET scans were negative in the remaining 4 patients tested. The proportion of patients with increased CSF p-tau181 and normal A beta 42 (A-T+) was significantly higher in NIID (75%) compared with DLB, PSP, and CBS (4.2%, 4.8%, and 7.7%, respectively). CSF HVA and 5-HIAA concentrations were significantly higher in patients with NIID compared with disease controls.DiscussionCSF p-tau181 was increased in patients with NIID without amyloid accumulation. Although the deposition of p-tau has not been reported in NIID brains, the molecular mechanism of tau phosphorylation or secretion of p-tau may be altered in NIID.

引用

页码：E1009 / E1019

页数：11

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