11C PIB PET Is associated with the brain biopsy amyloid-β load in subjects examined for normal pressure hydrocephalus

Juha O. Rinne*, Timo Suotunen, Jaana Rummukainen, Sanna Kaisa Herukka, Ossi Nerg, Anne M. Koivisto, Tuomas Rauramaa, Kjell Någren, Mikko Hiltunen, Irina Alafuzoff, Jaakko Rinne, Juha E. Jääskeläinen, Hilkka Soininen, Ville Leinonen

*Kontaktforfatter for dette arbejde

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Resumé

Background: Idiopathic normal pressure hydrocephalus (iNPH) is frequently associated with concomitant amyloid-β (Aβ) pathology. Objective: To compare the [ 11 C]PIB PET uptake in the patients with suspected iNPH to Aβ and hyperphosphorylated-tau (HPτ) in the right frontal cortical biopsy, the cerebrospinal fluid (CSF) Aβ, the response to a CSF shunt, and the final clinical diagnosis of Alzheimer's disease (AD). Methods: Patients (n = 21) from Kuopio NPH Registry (http://www.uef.fi/nph) with intraventricular pressure monitoring, immunostaining for Aβ and HPτ in the right frontal cortical biopsies, and a Mini-Mental State Examination and a Clinical Dementia Rating underwent [ 11 C]PIB PET. Aβ, total tau, and Pτ 181 were measured by ELISA from the ventricular (n = 15) and the lumbar (n = 9) CSF. Response to the shunt was seen in 13 out of the 15 shunted patients. AD was diagnosed in 8 patients during a median follow-up of 6 years (mean 7.3±2.4 years, range 3-1). Results: [ 11 C]PIB uptake in the right frontal cortex (ρ= 0.60, p < 0.01) and the combined neocortical [ 11 C]PIB uptake score (ρ= 0.61, p < 0.01) were associated with a higher Aβ load in the right frontal cortical biopsy. Excluding one (1/15) outlier, [ 11 C]PIB uptake was also associated with the ventricular CSF Aβ (ρ= -0.58, p = 0.03). Conclusions: The findings show that [ 11 C]PIB PET can reliably detect simultaneous amyloid pathology among the iNPH patients. Further studies will show whether amyloid PET could predict a clinical response to the shunt operation. In addition, the presence of Aβ pathology in the patients with iNPH might also warrant treatment with current AD drugs.

OriginalsprogEngelsk
TidsskriftJournal of Alzheimer's Disease
Vol/bind67
Udgave nummer4
Sider (fra-til)1343-1351
ISSN1387-2877
DOI
StatusUdgivet - 2019

Fingeraftryk

Normal Pressure Hydrocephalus
Cerebrospinal Fluid
Alzheimer Disease
Pathology
Ventricular Pressure
Registries
N-methyl-2-(4'-methylaminophenyl)-6-hydroxybenzothiazole
Pharmaceutical Preparations

Citer dette

Rinne, J. O., Suotunen, T., Rummukainen, J., Herukka, S. K., Nerg, O., Koivisto, A. M., ... Leinonen, V. (2019). 11C PIB PET Is associated with the brain biopsy amyloid-β load in subjects examined for normal pressure hydrocephalus. Journal of Alzheimer's Disease, 67(4), 1343-1351. https://doi.org/10.3233/JAD-180645
Rinne, Juha O. ; Suotunen, Timo ; Rummukainen, Jaana ; Herukka, Sanna Kaisa ; Nerg, Ossi ; Koivisto, Anne M. ; Rauramaa, Tuomas ; Någren, Kjell ; Hiltunen, Mikko ; Alafuzoff, Irina ; Rinne, Jaakko ; Jääskeläinen, Juha E. ; Soininen, Hilkka ; Leinonen, Ville. / 11C PIB PET Is associated with the brain biopsy amyloid-β load in subjects examined for normal pressure hydrocephalus. I: Journal of Alzheimer's Disease. 2019 ; Bind 67, Nr. 4. s. 1343-1351.
@article{7d1accdfd4a24ee88bfe2c5ef9134960,
title = "11C PIB PET Is associated with the brain biopsy amyloid-β load in subjects examined for normal pressure hydrocephalus",
abstract = "Background: Idiopathic normal pressure hydrocephalus (iNPH) is frequently associated with concomitant amyloid-β (Aβ) pathology. Objective: To compare the [ 11 C]PIB PET uptake in the patients with suspected iNPH to Aβ and hyperphosphorylated-tau (HPτ) in the right frontal cortical biopsy, the cerebrospinal fluid (CSF) Aβ, the response to a CSF shunt, and the final clinical diagnosis of Alzheimer's disease (AD). Methods: Patients (n = 21) from Kuopio NPH Registry (http://www.uef.fi/nph) with intraventricular pressure monitoring, immunostaining for Aβ and HPτ in the right frontal cortical biopsies, and a Mini-Mental State Examination and a Clinical Dementia Rating underwent [ 11 C]PIB PET. Aβ, total tau, and Pτ 181 were measured by ELISA from the ventricular (n = 15) and the lumbar (n = 9) CSF. Response to the shunt was seen in 13 out of the 15 shunted patients. AD was diagnosed in 8 patients during a median follow-up of 6 years (mean 7.3±2.4 years, range 3-1). Results: [ 11 C]PIB uptake in the right frontal cortex (ρ= 0.60, p < 0.01) and the combined neocortical [ 11 C]PIB uptake score (ρ= 0.61, p < 0.01) were associated with a higher Aβ load in the right frontal cortical biopsy. Excluding one (1/15) outlier, [ 11 C]PIB uptake was also associated with the ventricular CSF Aβ (ρ= -0.58, p = 0.03). Conclusions: The findings show that [ 11 C]PIB PET can reliably detect simultaneous amyloid pathology among the iNPH patients. Further studies will show whether amyloid PET could predict a clinical response to the shunt operation. In addition, the presence of Aβ pathology in the patients with iNPH might also warrant treatment with current AD drugs.",
keywords = "Amyloid, brain biopsy, cerebrospinal fluid, normal pressure hydrocephalus, positron emission tomography",
author = "Rinne, {Juha O.} and Timo Suotunen and Jaana Rummukainen and Herukka, {Sanna Kaisa} and Ossi Nerg and Koivisto, {Anne M.} and Tuomas Rauramaa and Kjell N{\aa}gren and Mikko Hiltunen and Irina Alafuzoff and Jaakko Rinne and J{\"a}{\"a}skel{\"a}inen, {Juha E.} and Hilkka Soininen and Ville Leinonen",
year = "2019",
doi = "10.3233/JAD-180645",
language = "English",
volume = "67",
pages = "1343--1351",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "I O S Press",
number = "4",

}

Rinne, JO, Suotunen, T, Rummukainen, J, Herukka, SK, Nerg, O, Koivisto, AM, Rauramaa, T, Någren, K, Hiltunen, M, Alafuzoff, I, Rinne, J, Jääskeläinen, JE, Soininen, H & Leinonen, V 2019, '11C PIB PET Is associated with the brain biopsy amyloid-β load in subjects examined for normal pressure hydrocephalus', Journal of Alzheimer's Disease, bind 67, nr. 4, s. 1343-1351. https://doi.org/10.3233/JAD-180645

11C PIB PET Is associated with the brain biopsy amyloid-β load in subjects examined for normal pressure hydrocephalus. / Rinne, Juha O.; Suotunen, Timo; Rummukainen, Jaana; Herukka, Sanna Kaisa; Nerg, Ossi; Koivisto, Anne M.; Rauramaa, Tuomas; Någren, Kjell; Hiltunen, Mikko; Alafuzoff, Irina; Rinne, Jaakko; Jääskeläinen, Juha E.; Soininen, Hilkka; Leinonen, Ville.

I: Journal of Alzheimer's Disease, Bind 67, Nr. 4, 2019, s. 1343-1351.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - 11C PIB PET Is associated with the brain biopsy amyloid-β load in subjects examined for normal pressure hydrocephalus

AU - Rinne, Juha O.

AU - Suotunen, Timo

AU - Rummukainen, Jaana

AU - Herukka, Sanna Kaisa

AU - Nerg, Ossi

AU - Koivisto, Anne M.

AU - Rauramaa, Tuomas

AU - Någren, Kjell

AU - Hiltunen, Mikko

AU - Alafuzoff, Irina

AU - Rinne, Jaakko

AU - Jääskeläinen, Juha E.

AU - Soininen, Hilkka

AU - Leinonen, Ville

PY - 2019

Y1 - 2019

N2 - Background: Idiopathic normal pressure hydrocephalus (iNPH) is frequently associated with concomitant amyloid-β (Aβ) pathology. Objective: To compare the [ 11 C]PIB PET uptake in the patients with suspected iNPH to Aβ and hyperphosphorylated-tau (HPτ) in the right frontal cortical biopsy, the cerebrospinal fluid (CSF) Aβ, the response to a CSF shunt, and the final clinical diagnosis of Alzheimer's disease (AD). Methods: Patients (n = 21) from Kuopio NPH Registry (http://www.uef.fi/nph) with intraventricular pressure monitoring, immunostaining for Aβ and HPτ in the right frontal cortical biopsies, and a Mini-Mental State Examination and a Clinical Dementia Rating underwent [ 11 C]PIB PET. Aβ, total tau, and Pτ 181 were measured by ELISA from the ventricular (n = 15) and the lumbar (n = 9) CSF. Response to the shunt was seen in 13 out of the 15 shunted patients. AD was diagnosed in 8 patients during a median follow-up of 6 years (mean 7.3±2.4 years, range 3-1). Results: [ 11 C]PIB uptake in the right frontal cortex (ρ= 0.60, p < 0.01) and the combined neocortical [ 11 C]PIB uptake score (ρ= 0.61, p < 0.01) were associated with a higher Aβ load in the right frontal cortical biopsy. Excluding one (1/15) outlier, [ 11 C]PIB uptake was also associated with the ventricular CSF Aβ (ρ= -0.58, p = 0.03). Conclusions: The findings show that [ 11 C]PIB PET can reliably detect simultaneous amyloid pathology among the iNPH patients. Further studies will show whether amyloid PET could predict a clinical response to the shunt operation. In addition, the presence of Aβ pathology in the patients with iNPH might also warrant treatment with current AD drugs.

AB - Background: Idiopathic normal pressure hydrocephalus (iNPH) is frequently associated with concomitant amyloid-β (Aβ) pathology. Objective: To compare the [ 11 C]PIB PET uptake in the patients with suspected iNPH to Aβ and hyperphosphorylated-tau (HPτ) in the right frontal cortical biopsy, the cerebrospinal fluid (CSF) Aβ, the response to a CSF shunt, and the final clinical diagnosis of Alzheimer's disease (AD). Methods: Patients (n = 21) from Kuopio NPH Registry (http://www.uef.fi/nph) with intraventricular pressure monitoring, immunostaining for Aβ and HPτ in the right frontal cortical biopsies, and a Mini-Mental State Examination and a Clinical Dementia Rating underwent [ 11 C]PIB PET. Aβ, total tau, and Pτ 181 were measured by ELISA from the ventricular (n = 15) and the lumbar (n = 9) CSF. Response to the shunt was seen in 13 out of the 15 shunted patients. AD was diagnosed in 8 patients during a median follow-up of 6 years (mean 7.3±2.4 years, range 3-1). Results: [ 11 C]PIB uptake in the right frontal cortex (ρ= 0.60, p < 0.01) and the combined neocortical [ 11 C]PIB uptake score (ρ= 0.61, p < 0.01) were associated with a higher Aβ load in the right frontal cortical biopsy. Excluding one (1/15) outlier, [ 11 C]PIB uptake was also associated with the ventricular CSF Aβ (ρ= -0.58, p = 0.03). Conclusions: The findings show that [ 11 C]PIB PET can reliably detect simultaneous amyloid pathology among the iNPH patients. Further studies will show whether amyloid PET could predict a clinical response to the shunt operation. In addition, the presence of Aβ pathology in the patients with iNPH might also warrant treatment with current AD drugs.

KW - Amyloid

KW - brain biopsy

KW - cerebrospinal fluid

KW - normal pressure hydrocephalus

KW - positron emission tomography

U2 - 10.3233/JAD-180645

DO - 10.3233/JAD-180645

M3 - Journal article

VL - 67

SP - 1343

EP - 1351

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 4

ER -