Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Amyloid. 2013 Jun;20(2):107-12. doi: 10.3109/13506129.2013.790810. Epub 2013 May 2.
We studied seven cases of Alzheimer's disease (AD). Six of the patients had presenilin 1 (PS1) mutations (PS1AD). Three novel PS1 mutations (T99A, H131R and L219R) and three other missense mutations (M233L, H163R and V272A) were found in the PS1AD group. We measured the levels of phosphorylated tau (ptau-181, ptau-199) and Aβ (Aβ1-42, Aβ1-40 and Aβ1-38) in the cerebrospinal fluid (CSF) of PS1AD patients, early-onset sporadic AD (EOSAD), late-onset sporadic AD (LOSAD) and non-demented subjects (ND). The CSF levels of Aβ1-42 in the three AD groups were significantly lower than those of the ND group (p < 0.0001). CSF levels of Aβ1-42 in the PS1AD group were significantly lower than those in the two sporadic AD groups. The Aβ1-40 and Aβ1-38 levels in the CSF of the PS1AD group were significantly lower than those of the three other groups (p < 0.0001, respectively). The levels of Aβ1-40, Aβ1-38 and Aβ1-42 in the CSF of the PS1AD group remained lower than those of the ND group for 4 years. Not only CSF Aβ1-42, but also Aβ1-40 and Aβ1-38 decreased in the advanced stages of PS1AD.
我们研究了 7 例阿尔茨海默病（AD）病例。其中 6 例患者存在早老素 1（PS1）突变（PS1AD）。在 PS1AD 组中发现了 3 种新的 PS1 突变（T99A、H131R 和 L219R）和 3 种其他错义突变（M233L、H163R 和 V272A）。我们测量了 PS1AD 患者、早发性散发性 AD（EOSAD）、晚发性散发性 AD（LOSAD）和非痴呆受试者（ND）脑脊液（CSF）中磷酸化 tau（ptau-181、ptau-199）和 Aβ（Aβ1-42、Aβ1-40 和 Aβ1-38）的水平。三组 AD 患者的 CSF Aβ1-42 水平明显低于 ND 组（p<0.0001）。PS1AD 组 CSF Aβ1-42 水平明显低于两例散发性 AD 组。PS1AD 组 CSF 中 Aβ1-40 和 Aβ1-38 水平明显低于其余三组（p<0.0001）。PS1AD 组 CSF 中 Aβ1-40、Aβ1-38 和 Aβ1-42 水平在 4 年内仍低于 ND 组。不仅 CSF Aβ1-42，而且 Aβ1-40 和 Aβ1-38 在 PS1AD 的晚期也会减少。
