Jia Jian-ping

PRNP mutations in a series of apparently sporadic neurodegenerative dementias in China.

Mutations in prion protein gene (PRNP) may lead to genetic prion disease, which usually has a broad range of phenotypic presentations that overlap with other neurodegenerative dementias. In this study, we screened the PRNP gene to evaluate the frequency of PRNP mutations and their correlations with clinical phenotype in 185 sporadic neurodegenerative dementia cases and 310 control subjects. Samples of DNA from each subject underwent polymerase chain reaction (PCR) amplification and direct sequencing of PRNP. The clinical characteristics of patients carrying PRNP mutations were detailed. We identified five different PRNP mutations in five patients, of which three were novel (S97N, F198V, and R208C) and two were known (D178N‐129M and M232R). The rate of PRNP mutation was 2.70% in our sample. Though future studies confirming the correlation between PRNP mutations and clinical phenotype need to be undertaken, PRNP genotyping may be a valuable tool to differentiate between prion disease and other neurodegenerative dementias. Am. J. Med. Genet.

Adhesion Molecules in Dementia

During the past decade it has become evident that immunological, infl ammatory and vascular processes play an important role in the etiology and pathogenesis of various neuro-degenerative diseases. Alzheimers disease (AD) is a complex and genetically heterogeneous disease that is the most common form of dementia and aff ects up to 15 million individuals worldwide. Th e presenting pathology of AD includes extacellular neuritic plaques composed of beta-amyloid peptide (As) and intracellular neurofi brillary tangles composed of hyperphosphorylated tau, with neuronal loss in specifi c brain regions. A large body of evidence suggests that some form(s) of the polymorphic As are neurotoxic and induce neuronal death, tau hyperphosphorylation and neuronal death. However, the mechanisms underlying these pathological changes are still largely unknown. Th e early stages of symptomatic AD are characterized by memory impairment and subtle behavioral changes that are associated with changes in synaptic function. Th e loss of synapses strongly correlates with cognitive decline in AD and is now thought to result from the interactions of toxic forms of As peptide with molecules that are essential for neuronal integrity and synaptic connections. A combination of cell culture and animal studies has recently shown that adhesion molecules play important roles in synapse initiation, maturation, and function. Functional studies of individual adhesion molecules have begun to provide information on their role in synapse assembly and synaptic plasticity. In this chapter, we review the roles of diff erent families of adhesion molecules, including the immunoglobulins, integrins, cadherins and selectins, in normal brain and in dementia, particularly Alzheimers disease. (Less)

Hearing Impairment in Senile Dementia of Alzhaimer's Type*

Abstract Objectives To evaluate peripheral auditory dysfunction in senile dementia of Alzheimer’s disease (AD) and its relationship with cognitive dysfunction. Methods Pure tone thresholds, word recognition scores (WRS), acoustic immittance and auditory brain-stem responses (ABR) were tested to evaluate the auditory function in 43 AD patients and 50 normal subjects. The test reliability in these subjects was examined before the test results were evaluated for their correlation with the Mini Mental State Examination (MMSE) score. Results There were no statistically significant differences in peripheral auditory functions between the two ears in the tested subjects or between the two groups when the auditometric results of the right ear were compared (P > 0.05). Also, there were no statistically significant differences between the two groups when audiometric test reliability, acoustic impedance and ABR results were compared (P > 0.05). Conclutions The pure tone audiometric threshold and WRS in AD patients are similar to those in comparable non-AD senile subjects. Peripheral auditory dysfunction is not related to cognitive dysfunction.