The Florey Institute,The University of Melbourne,Parkville,Victoria,Australia.
Centre of Excellence for Alzheimer's Disease Research and Care,Edith Cowan University,Joondalup,Western Australia,Australia.
Int Psychogeriatr. 2017 Nov;29(11):1825-1834. doi: 10.1017/S1041610217001284. Epub 2017 Jul 19.
The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippocampal volume (HV) over 36-54 months in preclinical Alzheimer's disease (AD). However, the extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g. serum) is unknown. We aimed to determine the effect of Aβ and the BDNF Val66Met polymorphism on levels of serum mBDNF, EM, and HV at baseline and over 18-months.
Non-demented older adults (n = 446) underwent Aβ neuroimaging and BDNF Val66Met genotyping. EM and HV were assessed at baseline and 18 months later. Fasted blood samples were obtained from each participant at baseline and at 18-month follow-up. Aβ PET neuroimaging was used to classify participants as Aβ- or Aβ+.
At baseline, Aβ+ adults showed worse EM impairment and lower serum mBDNF levels relative to Aβ- adults. BDNF Val66Met polymorphism did not affect serum mBDNF, EM, or HV at baseline. When considered over 18-months, compared to Aβ- Val homozygotes, Aβ+ Val homozygotes showed significant decline in EM and HV but not serum mBDNF. Similarly, compared to Aβ+ Val homozygotes, Aβ+ Met carriers showed significant decline in EM and HV over 18-months but showed no change in serum mBDNF.
While allelic variation in BDNF Val66Met may influence Aβ+ related neurodegeneration and memory loss over the short term, this is not related to serum mBDNF. Longer follow-up intervals may be required to further determine any relationships between serum mBDNF, EM, and HV in preclinical AD.
脑源性神经营养因子（BDNF）Val66Met 多态性 Met 等位基因在临床前阿尔茨海默病（AD）中加剧了淀粉样蛋白（Aβ）相关的情景记忆（EM）和海马体积（HV）下降，时间跨度为 36-54 个月。然而，Aβ+和 BDNF Val66Met 与 BDNF 的循环标志物（例如血清）之间的关系程度尚不清楚。我们旨在确定 Aβ和 BDNF Val66Met 多态性对基线和 18 个月时血清 mBDNF、EM 和 HV 水平的影响。
非痴呆的老年人（n=446）接受了 Aβ神经影像学和 BDNF Val66Met 基因分型。EM 和 HV 在基线和 18 个月后进行评估。每位参与者在基线和 18 个月随访时都采集了空腹血样。使用 Aβ PET 神经影像学将参与者分为 Aβ+或 Aβ-。
在基线时，Aβ+成年人的 EM 损伤更严重，血清 mBDNF 水平更低。BDNF Val66Met 多态性在基线时不影响血清 mBDNF、EM 或 HV。在考虑 18 个月时，与 Aβ- Val 纯合子相比，Aβ+ Val 纯合子的 EM 和 HV 明显下降，但血清 mBDNF 没有变化。同样，与 Aβ+ Val 纯合子相比，Aβ+ Met 携带者在 18 个月时的 EM 和 HV 明显下降，但血清 mBDNF 没有变化。
虽然 BDNF Val66Met 的等位基因变异可能会在短期内影响 Aβ+相关的神经退行性变和记忆丧失，但这与血清 mBDNF 无关。可能需要更长的随访时间来进一步确定临床前 AD 中血清 mBDNF、EM 和 HV 之间的任何关系。
