Synaptic development of layer V pyramidal neurons in the prenatal human prefrontal neocortex: a Neurolucida-aided Golgi study

The prefrontal neocortex is involved in many high cognitive functions in humans.Deficits in neuronal and neurocircuitry development in this part of the cerebrum have been associated with various neuropsychiatric disorders in adolescents and adults.There are currently little available data regarding prenatal dendrite and spine formation on projecting neurons in the human prefrontal neocortex.Previous studies have demonstrated that Golgi silver staining can identify neurons in the frontal lobe and visual cortex in human embryos.In the present study,five fetal brains,at 19,20,26,35,and 38 gestational weeks,were obtained via the body donation program at Xiangya School of Medicine,Central South University,China.Golgi-stained pyramidal neurons in layer V of Brodmann area 46 in fetuses were quantitatively analyzed using the Neurolucida morphometry system.Results revealed that somal size,total dendritic length,and branching points of these neurons increased from 26 to 38 gestational weeks.There was also a large increase in dendritic spines from 35 to 38 gestational weeks.These findings indicate that,in the human prefrontal neocortex,dendritic growth in layer V pyramidal neurons occurs rapidly during the third trimester of gestation.The use of human fetal brain tissue was approved by the Animal Ethics Committee of Xiangya School of Medicine,Central South University,China(approval No.2011-045)on April 5,2011.

Correlations Between Single Nucleotide Polymorphisms,Cognitive Dysfunction,and Postmortem Brain Pathology in Alzheimer's Disease Among Han Chinese

In this study, the distribution of five Alzheimer's disease(AD)-related single nucleotide polymorphisms(SNPs) in the Han population was examined in combination with the evaluation of clinical cognition and brain pathological analysis. The associations among SNPs,clinical daily cognitive states, and postmortem neuropathological changes were analyzed in 110 human brains from the Chinese Academy of Medical Sciences/Peking Union Medical College(CAMS/PUMC) Human Brain Bank.APOE ?4(OR = 4.482, P = 0.004), the RS2305421 GG genotype(adjusted OR = 4.397, P = 0.015), and the RS10498633 GT genotype(adjusted OR = 2.375,P = 0.028) were associated with a higher score on the ABC(Ab plaque score, Braak NFT stage, and CERAD neuritic plaque score) dementia scale. These results advance our understanding of the pathogenesis of AD,the relationship between pathological diagnosis and clinical diagnosis, and the SNPs in the Han population for future research.

Focal-type,but not Diffuse-type,Amyloid Beta Plaques are Correlated with Alzheimer’s Neuropathology,Cognitive Dysfunction,and Neuroinflammation in the Human Hippocampus

Amyloid beta(Aβ)plaques are one of the hallmarks of Alzheimer’s disease(AD).However,currently available anti-amyloid therapies fail to show effectiveness in the treatment of AD in humans.It has been found that there are different types of Aβplaque(diffuse and focal types)in the postmortem human brain.In this study,we aimed to investigate the correlations among different types of Aβplaque and AD-related neuropathological and cognitive changes based on a postmortem human brain bank in China.The results indicated that focal plaques,but not diffuse plaques,significantly increased with age in the human hippocampus.We also found that the number of focal plaques was positively correlated with the severity of AD-related neuropathological changes(measured by the“ABC”scoring system)and cognitive decline(measured by the Everyday Cognitive Insider Questionnaire).Furthermore,most of the focal plaques were co-localized with neuritic plaques(identified by Bielschowsky silver staining)and accompanied by microglial and other inflammatory cells.Our findings suggest the potential of using focal-type but not general Aβplaques as biomarkers for the neuropathological evaluation of AD.