Is ApoE ɛ 4 a good biomarker for amyloid pathology in late onset Alzheimer’s disease?

Amyloid plaques are pathological hallmarks of Alzheimer’s Disease(AD)and biomarkers such as cerebrospinal fluid(CSF)β-amyloid 1–42(Aβ1-42)and amyloid positron emission tomographic(PET)imaging are important in diagnosing amyloid pathology in vivo.ɛ4 allele of the Apolipoprotein E gene(ApoEɛ4),which is a major genetic risk factor for late onset AD,is an important genetic biomarker for AD pathophysiology.It has been shown that ApoEɛ4 is involved in Aβdeposition and formation of amyloid plaques.Studies have suggested the utility of peripheral blood ApoEɛ4 in AD diagnosis and risk assessment.However it is still a matter of debate whether ApoEɛ4 status would improve prediction of amyloid pathology and represent a cost-effective alternative to amyloid PET or CSF Aβin resource-limited settings in late onset AD.Recent research suggest that the mean prevalence of PET amyloid-positivity is 95%in ApoEɛ4-positive AD patients.This short review aims to provide an updated information on the relationship between ApoEɛ4 and amyloid biomarkers.

Expert Consensus on Clinical Diagnostic Criteria for Fatal Familial Insomnia

INTRODUCTION Fatal familial insomnia （FFI） is a serious and rare prion disease, which was first reported by Lugaresi et al. in 1986.Early diagnosis of FFI might be important for early and sufficient counseling of patients and their relatives, also concerning the risk of inheritance, and potentially also for treatment studies. However, the diagnosis of FFI might be difficult because of the heterogeneity of clinical features, low sensitivity of diagnostic tests, and absence of family history. The aim of the present study was to develop a clinical scheme and diagnostic criteria for FFI based on our research and expert consensus.

Prevention strategies for Alzheimer’s disease

Symptomatic treatment during the dementia stage of Alzheimer’s disease(AD)cannot delay or halt the progression of this disease.Therefore,prevention in the preclinical stage is likely the most effective way to decrease the incidence of this age-associated neurodegenerative condition,and its associated burden for individuals and society.Age,gender,family history,ApoE4,systolic blood pressure,body mass index,total cholesterol level and physical activity are all used as component of dementia risk score.There have been numerous challenges in conducting primary prevention trials in AD.Enrichment strategies for prevention studies include studying those subjects with more risk factors for AD,such as older age,those with a positive family history of late onset AD,and those who are ApoE4 positive.Each of these strategies is designed to increase the probability of developing AD thereby decreasing the sample size or the duration of follow up.Another strategy would be to target directly the pathophysiology of AD in its preclinical stages and use the biomarkers in prevention trial as surrogate markers.This will be done first in carriers of dominantly inherited early onset AD.As this research takes place networks of memory clinics must prepare to transfer new knowledge to persons interested in a preventive approach to AD.

Neuropsychiatric symptoms are early indicators of an upcoming metabolic decline in Alzheimer's disease

Background:Neuropsychiatric symptoms(NPS)are increasingly recognized as early non-cognitive manifestations in the Alzheimer's disease(AD)continuum.However,the role of NPS as an early marker of pathophysiological progression in AD remains unclear.Dominantly inherited AD(DIAD)mutation carriers are young individuals who are destined to develop AD in future due to the full penetrance of the genetic mutation.Hence,the study of DIAD mutation carriers enables the evaluation of the associations between pure AD pathophysiology and metabolic correlates of NPS without the confounding effects of co-existing pathologies.In this longitudinal study,we aimed to identify regional brain metabolic dysfunctions associated with NPS in cognitively intact DIAD mutation carriers.Methods:We stratified 221 cognitively intact participants from the Dominantly Inherited Alzheimer's Network according to their mutation carrier status.The interactions of NPS measured by the Neuropsychiatric Inventory-Questionnaire(NPI-Q),age,and estimated years to symptom onset(EYO)as a function of metabolism measured by[^(18)F]flurodeoxyglucose([^(18)F]FDG)positron emission tomography,were evaluated by the mixed-effects regression model with family-level random effects in DIAD mutation carriers and non-carriers.Exploratory factor analysis was performed to identify the neuropsychiatric subsyndromes in DIAD mutation carriers using the NPI-Q subcomponents.Then the effects of interactions between specific neuropsychiatric subsyndromes and EYO on metabolism were evaluated with the mixed-effects regression model.Results:A total of 119 mutation carriers and 102 non-carriers were studied.The interaction of higher NPI-Q and shorter EYO was associated with more rapid declines of global and regional[18F]FDG uptake in the posterior cingulate and ventromedial prefrontal cortices,the bilateral parietal lobes and the right insula in DIAD mutation carriers.The neuropsychiatric subsyndromes of agitation,disinhibition,irritability and depression interacted with the EYO to drive the[^(18)F]FDG uptake decline in the DIAD mutation carriers.The interaction of NPI and EYO was not associated with[^(18)F]FDG uptake in DIAD mutation non-carriers.Conclusions:The NPS in cognitively intact DIAD mutation carriers may be a clinical indicator of subsequent metabolic decline in brain networks vulnerable to AD,which supports the emerging conceptual framework that NPS represent early manifestations of neuronal injury in AD.Further studies using different methodological approaches to identify NPS in predinical AD are needed to validate our findings.

阿尔茨海默病现状及展望

Aging is an undeniable fact of life and the global population is aging to a historically unprecedented degree. The population aged65 years or older comprises 750 million people, representing nearly 10%of the global population. As a result of prolonged life expectancy and falling mortality rates, China has become one of the most rapidly aging countries in the world, even surpassing several high-income countries in North America and Europe.