Change of Amyloid-ß 1-42 Toxic Conformer Ratio After Cerebrospinal Fluid Diversion Predicts Long-Term Cognitive Outcome in Patients with Idiopathic Normal Pressure Hydrocephalus.
J Alzheimers Dis
; 63(3): 989-1002, 2018.
Article
em En
| MEDLINE
| ID: mdl-29710721
ABSTRACT
BACKGROUND:
Alzheimer's disease (AD) pathology in idiopathic normal pressure hydrocephalus (iNPH) contributes to poor shunt responses. Amyloid-ß 1- 42 (Aß42) toxic conformer was recently identified with features of rapid oligomerization, strong neurotoxicity and synaptotoxicity.OBJECTIVE:
This observational study points to Aß42 toxic conformer as a biomarker for AD pathology and for poor postoperative prognosis in patients with iNPH.METHODS:
The first cohort consisted of patients with AD (nâ=â17) and iNPH (nâ=â17), and cognitively normal individuals (CN, nâ=â12). The second cohort, consisted of 51 patients with iNPH, was divided into two groups according to phosphorylated Tau (pTau) level (low- and high-pTau groups); the low-pTau group was further subdivided according to one-year postoperative change in Aß42 toxic conformer ratio (%) [Aß42 toxic conformer/Aß42×100] (decreased- and increased-conformer subgroups). Enzyme-linked immunosorbent assay was used to measure pTau, Aß42, and Aß42 toxic conformer in cerebrospinal fluid. Outcomes were evaluated using neuropsychological tests one- and two-years postoperatively.RESULTS:
In the first cohort, Aß42 toxic conformer ratio in the iNPH group (10.8%) was significantly higher than that in the CN group (6.3%) and significantly lower than that in the AD group (17.2%). In the second cohort, the high-pTau group showed cognitive decline two-years postoperatively compared to baseline. However, the low-pTau group showed favorable outcomes one-year postoperatively; furthermore, the increased-conformer subgroup showed cognitive decline two-years postoperatively while the decreased-conformer subgroup maintained the improvement.CONCLUSIONS:
Change in Aß42 toxic conformer ratio predicts long-term cognitive outcome in iNPH, even in the low-pTau group.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Peptídeos beta-Amiloides
/
Transtornos Cognitivos
/
Doença de Alzheimer
/
Hidrocefalia de Pressão Normal
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article