No abstract

Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated

No abstract

The current development of immunotherapy for Alzheimer's disease is based on the assumption that human-derived amyloid ␤ protein (A␤) can be targeted in a similar manner to animal cell-derived or synthetic A␤. Because the structure of A␤ depends on its source and the presence of cofactors, it is of great interest to determine whether human-derived oligomeric A␤ species impair brain function and, if so, whether or not their disruptive effects can be prevented using antibodies. We report that untreated ex vivo human CSF that contains A␤ dimers rapidly inhibits hippocampal long-term potentiation in vivo and that acute systemic infusion of an anti-A␤ monoclonal antibody can prevent this disruption of synaptic plasticity. A␤ monomer isolated from human CSF did not affect long-term potentiation. These results strongly support a strategy of passive immunization against soluble A␤ oligomers in early Alzheimer's disease.

No abstract

The standardization and clinical validation of the measurement of beta-amyloid(1-42) (Abeta42) in cerebrospinal fluid (CSF), plasma and urine is described using a commercially available sandwich-type ELISA with 21F12 and 3D6 as monoclonal antibodies. The INNOTEST beta-amyloid(1-42) allows the specific and reliable measurement of(1-42) amyloid peptides in CSF and plasma. The Abeta42 concentrations in serum and urine were below the detection limit. In plasma, no differences were found in Abeta42 levels between controls and patients with different neurodegenerative disorders (Alzheimer's disease (AD), Lewy body disease (LBD), others). In contrast, CSF-Abeta42 concentrations were lower in AD and LBD patients as compared to controls. No correlation was found in AD patients between CSF and plasma concentrations of Abeta42 or between CSF Abeta42 levels and blood-brain-barrier function. The quantitative outcome of the test is in part dependent on confounding factors such as tube type, freeze/thaw cycles, temperature of incubation, standard preparation protocol, and antibody selection. Notwithstanding these aspects, it emerged that Abeta42 is a useful biochemical marker for the diagnosis of AD patients, but there is a need for an international Abeta standard, a universally accepted protocol for CSF preparation, and a thorough evaluation of assay performance in function of the boundary conditions.

The VICCCS-2 suggests standardized use of the National Institute of Neurological Disorders-Canadian Stroke Network recommendations on neuropsychological and imaging assessment for diagnosis of VCI so as to promote research collaboration.

No abstract