Therapeutic approaches for prevention or reduction of amyloidosis are currently a main objective in basic and clinical research on Alzheimer's disease. Among the agents explored in clinical trials are anti-Aβ peptide antibodies and secretase inhibitors. Most anti-Aβ antibodies are considered to act via inhibition of amyloidosis and enhanced clearance of existing amyloid, although secretase inhi...

Amyloid-beta peptide (Aβ)-directed active and passive immunization therapeutic strategies reduce brain levels of Aβ, decrease the severity of beta-amyloid plaque pathology and reverse cognitive deficits in mouse models of Alzheimer's disease (AD). As an alternative approach to passive immunization with full IgG molecules, single-chain variable fragment (scFv) antibodies can modulate or neutrali...

Brain-derived neurotrophic factor (BDNF) is a versatile neurotrophic factor that has been implicated in cell survival, cell differentiation, axonal growth, and activity-dependent synaptic plasticity. Changes in BDNF expression have also been reported during the course of several neurological disorders, including Alzheimer's disease (AD). The role of BDNF in AD, however, has remained elusive. To...

Amyloid A plaques are a key pathologic feature of Alzheimer disease (AD), but whether plaque sizes increase or stabilize over the course of AD is unknown. We measured the size distribution of total immunoreactive (10D5-positive) and dense-core (Thioflavin SYpositive) plaques in the temporal neocortex of a large group of subjects with AD and age-matched plaque-bearing subjects without dementia t...

Recent development in molecular imaging enables measurement of fibrillar amyloid plaque in Alzheimer (AD) brain using positron emission tomography (PET). Three tracers (florbetapir, flutemetamol, florbetaben) have been approved by FDA and EMA for use in clinical assessment of memory impairment to exclude AD. The use of amyloid PET imaging is considered to be appropriate in patients with persist...

Passive immunization against misfolded toxic proteins is a promising approach to treat neurodegenerative disorders. For effective immunotherapy against Alzheimer's disease, recent clinical data indicate that monoclonal antibodies directed against the amyloid-β peptide should be administered before the onset of symptoms associated with irreversible brain damage. It is therefore critical to devel...

Alzheimer's disease is a neurodegenerative disorder typified by the accumulation of a small protein, beta-amyloid, which aggregates and is the primary component of amyloid plaques. Many new therapeutic and diagnostic agents for reducing amyloid plaques have limited efficacy in vivo because of poor transport across the blood-brain barrier. Here we demonstrate that low-intensity focused ultrasoun...

Passive immunization against misfolded toxic proteins is a promising approach to treat neurodegenerative disorders. For effective immunotherapy against Alzheimer’s disease, recent clinical data indicate that monoclonal antibodies directed against the amyloid-b peptide should be administered before the onset of symptoms associated with irreversible brain damage. It is therefore critical to devel...

15.1 Introduction Alzheimer's disease (AD), a progressive neurovegetative disorder of the central nervous system and a leading cause of dementia, is partially caused by genetic changes. The molecular mechanisms and hypothesis of AD is very complex. The key event leading to AD appears to be the formation of a peptide known as amyloid beta (Aß) which clusters into amyloid plaques or senile plaque...

IMPORTANCE While numerous genetic susceptibility loci have been identified for clinical Alzheimer disease (AD), it is important to establish whether these variants are risk factors for the underlying disease pathology, including neuritic plaques. OBJECTIVES To investigate whether AD susceptibility loci from genome-wide association studies affect neuritic plaque pathology and to additionally i...