In vivo staging of regional amyloid deposition

نویسندگان

  • Michel J. Grothe
  • Henryk Barthel
  • Jorge Sepulcre
  • Martin Dyrba
  • Osama Sabri
  • Stefan J. Teipel
چکیده

OBJECTIVES To estimate a regional progression pattern of amyloid deposition from cross-sectional amyloid-sensitive PET data and evaluate its potential for in vivo staging of an individual's amyloid pathology. METHODS Multiregional analysis of florbetapir (18F-AV45)-PET data was used to determine individual amyloid distribution profiles in a sample of 667 participants from the Alzheimer's Disease Neuroimaging Initiative cohort, including cognitively normal older individuals (CN) as well as patients with mild cognitive impairment and Alzheimer disease (AD) dementia. The frequency of regional amyloid positivity across CN individuals was used to construct a 4-stage model of progressing amyloid pathology, and individual distribution profiles were used to evaluate the consistency of this hierarchical stage model across the full cohort. RESULTS According to a 4-stage model, amyloid deposition begins in temporobasal and frontomedial areas, and successively affects the remaining associative neocortex, primary sensory-motor areas and the medial temporal lobe, and finally the striatum. Amyloid deposition in these brain regions showed a highly consistent hierarchical nesting across participants, where only 2% exhibited distribution profiles that deviated from the staging scheme. The earliest in vivo amyloid stages were mostly missed by conventional dichotomous classification approaches based on global florbetapir-PET signal, but were associated with significantly reduced CSF Aβ42 levels. Advanced in vivo amyloid stages were most frequent in patients with AD and correlated with cognitive impairment in individuals without dementia. CONCLUSIONS The highly consistent regional hierarchy of PET-evidenced amyloid deposition across participants resembles neuropathologic observations and suggests a predictable regional sequence that may be used to stage an individual's progress of amyloid pathology in vivo.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Effect of Long-term Exposure to Extremely Low-frequency Electromagnetic Fields on β-amyloid Deposition and Microglia Cells in an Alzheimer Model in Rats

Background: Recently, researchers have considered extremely low-frequency electromagnetic fields (ELF-EMFs), as one of the non-invasive therapies, in the treatment of many severe neurological disorders, including Alzheimer Disease (AD). AD is a progressive neurodegenerative disease characterized by the deposition of amyloid plaques in the brain. However, the increase in microglial cells increas...

متن کامل

LRP-1 polymorphism is associated with global and regional amyloid load in Alzheimer's disease in humans in-vivo

OBJECTIVE Impaired amyloid clearance has been proposed to contribute to β-amyloid deposition in sporadic late-onset Alzheimer's disease (AD). Low density lipoprotein receptor-related protein 1 (LRP-1) is involved in the active outward transport of β-amyloid across the blood-brain barrier (BBB). The C667T polymorphism (rs1799986) of the LRP-1 gene has been inconsistently associated with AD in ge...

متن کامل

Comparing the Impact of Long-Term Exposure to Extremely Low-Frequency Electromagnetic Fields With Diverse Values on Anxiety, Memory, Learning, and Β-Amyloid Deposition in Adult Rats

Background: Extremely low-frequency electromagnetic fields (ELF-EMFs) have gathered significant consideration for their possible pathogenicity. However, their effects on nervous system functions were not fully clarified. In this study, our aim was to assay the effect of ELF-EMFs with different intensity on memory, anxiety, antioxidant activity, beta amyloid (Aβ) deposition and microglia populat...

متن کامل

Mechanisms of Brain Region-Specific Amyloid-beta Deposition

Alzheimer's disease (AD) is the most common cause of dementia. A fundamental feature of AD is brain region-specific deposition of extracellular amyloid plaques principally comprised of the amyloid-β (Aβ) peptide. Using mouse models of cerebral Aβ deposition, we examined molecular, cellular and systems-level mechanisms that regulate brain region-specific Aβ accumulation and aggregation. Parallel...

متن کامل

Clinical validity of A beta-protein deposition staging in brain aging and Alzheimer disease.

Braak's neurofibrillary tangle (NFT) pathology staging system of Alzheimer disease (AD) correlates generally with clinical data. Recently, Braak's group proposed an Abeta-protein staging based on the progression of amyloid deposition in the medial temporal lobe. To examine its clinical validity and evaluate whether it adds predictive power to NFT-based staging, we performed a study comparing bo...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 89  شماره 

صفحات  -

تاریخ انتشار 2017