Effect of the electro-acupuncture on senile plaques and its formation in APPD/PS1D double transgenic mice

Alzheimer’s disease(AD)is a progressive neurodegenerative disease and its incidence will increase with age and is aggravating.The senile plaques(SPs)are one of three main pathological features in AD patients,which are formed by amyloid b-protein(Ab)overaccumulation.b-amyloid precursor protein(APP),b-site APP cleavage(BACE1),and insulin degrading enzyme(IDE)proteins participate in the process of Ab production and degradation.At present,the pathogenesis of AD is not yet clear and the current treatment methods can only relief the related symptoms of AD.The electro-acupuncture(EA)is a traditional Chinese medicine treatment combined the acupuncture and electrical stimulation and the treatment effect can also be controlled by transform the electrical frequency.Thus,in this experiment,we carried out behavioral test,immunohistochemistry(IHC),and Western Blot(WB)after different period treatments to the model mice by electro-acupuncturing“Baihui”and“Shenshu”acupoints in APPt/PS1t double transgenic mice.It was found that the EA therapy can improve the ability of learning,memory and spatial exploration,and reduce the deposition of SPs in brain of AD model mice,and reduce the expressions of APP and BACE1,increase the expression of IDE protein.These results prompt that EA can effectively alleviate the pathological process of AD.We speculate that EA may play a comprehensive role in preventing the development of AD,considering the previous data.

A peptide-based near-infrared fluorescence probe for dynamic monitoring senile plaques in Alzheimer＇s disease mouse model

In vivo monitoring neuropathological changes in Alzheimer's disease(AD) animal model is critical for drug development. Here, by integrating blood-brain barrier penetrable peptide, we have developed a peptide probe which based on angiopep-2. Angiopep-based probe exhibited high binding affinity to Ab aggregates and labeled senile plaques in vivo. Remarkably, the in vivo near-infrared imaging data revealed that fluorescence signals of this probe were nearly 3-fold higher in the brains of 16-monthold APP/PS1 transgenic mice compared to C57 mice and exhibited linear correlation with the senile plaques load process in 4-, 8-, 16-month-old APP/PS1 transgenic mice. Moreover, senile plaques load was detected in vivo as early as 4 months of age that even at the very beginning of plaques developed in APP/PS1 transgenic mice. Taken together, this novel peptide-based probe achieved dynamic monitoring senile plaques in APP/PS1 transgenic mice and have been ready to use in drug development in AD mouse model.

Degenerative alterations in noradrenergic neurons of the locus coeruleus in Alzheimer's disease

Mice carrying mutant amyloid precursor protein and presenilin-1 genes （APP/PS1 double trans- genic mice） have frequently been used in studies of Alzheimer＇s disease; however, such studies have focused mainly on hippocampal and cortical changes. The severity of Alzheimer＇s disease is known to correlate with the amount of amyloid-13 protein deposition and the number of dead neurons in the locus coeruleus. In the present study, we assigned APP/PS1 double transgenic mice to two groups according to age： young mice （5-6 months old） and aged mice （16-17 months old）. Age-matched wild-type mice were used as controls. Immunohistochemistry for tyrosine hydroxylase （a marker of catecholaminergic neurons in the locus coeruleus） revealed that APP/PS1 mice had 23% fewer cells in the locus coeruleus compared with aged wild-type mice. APP/PS1 mice also had increased numbers of cell bodies of neurons positive for tyrosine hydroxylase, but fewer tyrosine hydroxylase-positive fibers, which were also short, thick and broken. Quantitative analysis using unbiased stereology showed a significant age-related increase in the mean volume of tyrosine hy- droxylase-positive neurons in aged APP/PS1 mice compared with young APP/PS1 mice. Moreover, the mean volume of tyrosine hydroxylase-positive neurons was positively correlated with the total volume of the locus coeruleus. These findings indicate that noradrenergic neurons and fibers in the locus coeruleus are predisposed to degenerative alterations in APP/PS1 double transgenic mice.

Apolipoprotein A1,the neglected relative of Apolipoprotein E and its potential role in Alzheimer’s disease

Lipoproteins are multi-molecule assemblies with the primary function of transportation and processing of lipophilic substances within aqueous bodily fluids(blood,cerebrospinal fluid).Nevertheless,they also exert other physiological functions such as immune regulation.In particular,neurons are both sensitive to uncontrolled responses of the immune system and highly dependent on a controlled and sufficient supply of lipids.For this reason,the role of certain lipoproteins and their protein-component(apolipoproteins,Apo’s)in neurological diseases is perceivable.ApoE,for example,is well-accepted as one of the major risk factors for sporadic Alzheimer’s disease with a protective allele variant(ε2)and a risk-causing allele variant(ε4).ApoA1,the major protein component of high-density lipoproteins,is responsible for transportation of excess cholesterol from peripheral tissues to the liver.The protein is synthesized in the liver and intestine but also can enter the brain via the choroid plexus and thereby might have an impact on brain lipid homeostasis.This review focuses on the role of ApoA1 in Alzheimer’s disease and discusses whether its role within this neurodegenerative disorder is specific or represents a general neuroprotective mechanism.

Imaging and Spectral Characteristics of Amyloid Plaque Autofluorescence in Brain Slices from the APP/PS1 Mouse Model of Alzheimer’s Disease

Amyloid deposits are one of the hallmark pathological lesions of Alzheimer's disease(AD). They can be visualized by thioflavin-S, silver impregnation,Congo red staining, and immunohistochemical reactions.However, that amyloid deposits generate blue autofluorescence(auto-F) has been ignored. Here, we report that visible light-induced auto-F of senile plaques(SPs) was detected and validated with conventional methods. Brain slices from APP/PS1(amyloid precursor protein/presenilin1) transgenic mice were mounted on slides, rinsed,coverslipped and observed for details of the imaging and spectral characteristics of the auto-F of SPs. Then the slices were treated with the above classic methods for comparative validation. We found that the SP auto-F was greatest under blue-violet excitation with a specific emission spectrum, and was much easier, more sensitive, and reliable than the classic methods. Because it does not damage slices, observation of auto-F can be combined with all post-staining techniques in slices and for brain-wide imaging in AD.