There are many active research projects accessing and applying shared ADNI data. Use the search above to find specific research focuses on the active ADNI investigations. This information is requested annually as a requirement for data access.
| Principal Investigator | |
| Principal Investigator's Name: | Rui Li |
| Institution: | Huashan Hospital, Fudan University |
| Department: | Neurology |
| Country: | |
| Proposed Analysis: | Vascular contributions to dementia and Alzheimer's disease (AD) are increasingly recognized as shown by neuropathological, neuroimaging, and cerebrospinal fluid biomarker studies. Recent studies have demonstrated that blood-brain barrier (BBB) breakdown is an early biomaker of AD, prior to neurodegeneration and neuropathology. Impaired BBB integrity involved in compromised transport systems or cellular junctions was shown to contribute to brain Aβ deposition, which is one of the major drivers of AD, with diminished clearance of Aβ. The removal of soluble Aβ from the brain occurs via various overlapping clearance systems, including transport across degradation, BBB, cerebrospinal fluid (CSF) absorption and interstitial fluid (ISF) bulk flow clearance, in which BBB pathway was deemed to be the predominant. To data, the extent to which each of these pathways contributes to elimination of Aβ from the brain still remains unclear but impaired perivascular clearance of Aβ have been recognized as an importance role in the pathogenesis of AD. The perivascular drainage pathway and CSF sink clearance constitute the ISF bulk flow clearance and the former is the movement of small solutes along the ISF and into the spaces that surround cerebral microvessels, which are called perivascular spaces or Virchow-Robin spaces. Currently, there are two perivascular drainage pathways that have been proposed: the intramural periarterial drainage (IPAD) and glymphatic clearance pathway. As mainly described in studies, the IPAD pathway involves periarterial space without paravenous space while the glymphatic system involves a periarterial CSF influx route, a paravenous ISF clearance route through the perivenous space, and an intracellular transastrocytic path that couples the two extracellular paravascular routes. Although both arteries and veins are involved in Aβ drainage, research has been primarily focused on arterial Aβ, while the accumulation of Aβ in veins and venules were to a lesser extent. A controversy remains about the contribution of Aβ within different vessel walls. Currently, preclinical and clinical studies demonstrated the presence of venular amyloid, the deposition of Aβ within veins and venules. The accumulation of Aβ along the venous system occurs to a greater degree than previously thought. Venular amyloid is likely an integral part of AD pathogenesis, and similar to arterial amyloid, contributes to cerebrovascular dysfunction and failure of Aβ clearance mechanisms. In addition, Banerjee and colleagues suggest that MRI-visible perivascular spaces in Alzheimer’s disease are a result of cerebrovascular dysfunction, specifically small vessel disease co-morbidities, as they observed no association between amyloid burden and perivascular space enlargement, the perivascular space was independently of amyloid burden. However, others have reported strong associations; amyloid positron emission tomography (PET) and histopathology measurements colocalized with enlarged cortical perivascular spaces in cases of AD. As such, we hypothesized that brain amyloid burden would be associated with enlarged perivenous spaces, as detected by susceptibility-weighted imaging (SWI) and T2-weighted magnetic resonance imaging (MRI). The amyloid deposition was measured by amyloid positron emission tomography using 11C-Pittsburgh B compound (PiB-PET). This study may provide supportable imaging evidence for contribution of venular amyloid to AD pathogenesis. |
| Additional Investigators |
