Peng Shiyong, Wuu Joanne, Mufson Elliott J, Fahnestock Margaret
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
J Neuropathol Exp Neurol. 2004 Jun;63(6):641-9. doi: 10.1093/jnen/63.6.641.
Nerve growth factor (NGF) is critical for the regulation, differentiation, and survival of basal forebrain cholinergic neurons that degenerate in the late stage of Alzheimer disease (AD). The precursor of NGF (proNGF) is the predominant form of NGF in brain and is increased in end stage AD. To determine whether this increase in proNGF is an early or late change during the progression of cognitive decline, we used Western blotting to measure the relative amounts of proNGF protein in the parietal cortex from subjects clinically classified with no cognitive impairment (NCI; n = 20), mild cognitive impairment (MCI; n = 20), or mild to moderate AD (n = 19). We found that proNGF increased during the prodromal stage of AD. The amount of proNGF protein was 1.4-fold greater in the MCI group as compared to NCI, and was 1.6-fold greater in mild-moderate AD as compared to NCI, similar to our previous findings of a 2-fold increase in end stage AD. There was a negative correlation between proNGF levels and Mini Mental Status Examination (MMSE) score, demonstrating that the accumulation of proNGF is correlated with loss of cognitive function. These findings demonstrate that proNGF levels increase during the preclinical stage of AD and may reflect an early biological marker for the onset of AD.
神经生长因子（NGF）对于基底前脑胆碱能神经元的调节、分化和存活至关重要，而这些神经元在阿尔茨海默病（AD）晚期会发生退化。NGF的前体（proNGF）是大脑中NGF的主要形式，在AD终末期会增加。为了确定proNGF的这种增加是认知衰退进展过程中的早期还是晚期变化，我们使用蛋白质印迹法测量了临床分类为无认知障碍（NCI；n = 20）、轻度认知障碍（MCI；n = 20）或轻度至中度AD（n = 19）的受试者顶叶皮质中proNGF蛋白的相对含量。我们发现proNGF在AD前驱期增加。与NCI相比，MCI组中proNGF蛋白的量增加了1.4倍，与NCI相比，轻度至中度AD组中增加了1.6倍，这与我们之前在AD终末期发现的2倍增加相似。proNGF水平与简易精神状态检查表（MMSE）评分呈负相关，表明proNGF的积累与认知功能丧失相关。这些发现表明，proNGF水平在AD临床前期增加，可能反映了AD发病的早期生物学标志物。
