Current Alzheimer Research - Volume 3, Issue 5, 2006

Current Alzheimer Research presents the fifth issue of its third volume and this special issue is meant to mark the centennial of Alois Alzheimer 's original de-scription of the disease that would come to bear his name. How best can one commemorate this seminal discovery' Since the field has become quite diverse and large, it is difficult to accommodate all the fasci-nating areas of Alzheimer's disease (AD), nor could we invite Read More

Alzheimer's disease (AD) is the most common type of dementia in the US and much of the world with rates increasing exponentially from age 65. Increases in life expectancy in the last century have resulted in a large number of people living to old ages and will result in a quadrupling of AD cases by the middle of the century. Preventing or delaying the onset of AD could have a huge impact in the number of cases expected t Read More

Advances in the understanding of Alzheimer's disease (AD) pathogenesis provide strong support for a modified version of the amyloid cascade hypothesis, which is now often referred to as the amyloid β protein (Aβ) cascade hypothesis. The basic tenant of this modified hypothesis is that Aβ aggregates trigger a complex pathological cascade leading to neurodegeneration. Thus, as opposed to the original amyloid hypothesis, Read More

Proteases have long played a central role in the molecular pathogenesis of Alzheimer’s disease (AD), yet proteases that degrade the amyloid β-protein (Aβ) itself were largely ignored until only quite recently. Today, we know that Aβ-degrading proteases are critical regulators of brain Aβ levels in vivo, with evidence accumulating that their dysfunction may play a role in the etiology of AD. This review explores the historical Read More

Since the initial description one hundred years ago by Dr. Alois Alzheimer, the disorder that bears his name has been characterized by the occurrence of two brain lesions: amyloid plaques and neurofibrillary tangles (NFTs). Yet the precise relationship between beta-amyloid (Aβ) and tau, the two proteins that accumulate within these lesions, has proven elusive. Today, a growing body of work supports the notion that Aβ ma Read More

The microtubule-associated protein tau, which is abundantly expressed in neurons, is deposited in cells in an abnormally phosphorylated state as fibrillar lesions in numerous neurodegenerative diseases, with the most notable being Alzheimer's disease. Tau plays a crucial role in the neuron as it binds and stabilizes microtubules, and can regulate axonal transport; functions that are regulated by site-specific phosphorylation eve Read More

As a group, strains of laboratory mice carrying Alzheimer's disease (AD)-related transgenes are currently the most widely studied animal models of AD. Many AD mouse models carrying the same or similar transgene constructs demonstrate strikingly different phenotypic responses to transgene expression, mimicking the apparent genetic complexity of AD pathogenesis seen in the human population. Genetic differences between Read More

Major hallmarks of Alzheimer's disease (AD) include brain deposition of the amyloid-β peptide (Aβ), which is proteolytically cleaved from a large Aβ precursor protein (APP) by β and β- secretases. A transmembrane aspartyl protease, β-APP cleaving enzyme (BACE1), has been recognized as the β-secretase. We review the structure and function of the BACE1 protein, and of 4129 bp of the 5'-flanking region sequence of the BACE1 Read More

Two genetically distinct types of frontotemporal dementia (FTD) are linked to chromosome 17q21. FTD with parkinsonism (FTDP-17) results from mutations in the gene encoding microtubule associated protein tau (MAPT) and is associated with tau deposition in the patient's brain. An increasing number of FTD families are linked to 17q21 in the absence of a demonstrable MAPT mutation. Brains of these patients do not show tau Read More

Pathological folding and aggregation of the amyloid β-protein (Aβ) are widely perceived as central to understanding Alzheimer's disease (AD) at the molecular level. Experimental approaches to study Aβ self-assembly are limited, because most relevant aggregates are quasi-stable and inhomogeneous. In contrast, simulations can provide significant insights into the problem, including specific sites in the molecule that wo Read More

Neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD) afflict growing numbers of people but treatments are not available or ineffective. These diseases are characterized by the loss of specific neuronal populations, the accumulation of protein aggregates inside and sometimes outside neurons, and an activation of immune pathways in the brain. The causes of sporadic forms of AD or PD ar Read More

Mitochondrial dysfunction has been implicated in causing metabolic abnormalities in Alzheimer's disease (AD). The searches for mitochondrial DNA variants associated with AD susceptibility have generated conflicting results. The age-related accumulation of somatic mitochondrial DNA deletion has been suggested to play a pathogenic role in the development of AD. Recent studies have demonstrated that amyloid-beta peptide ( Read More

Down syndrome (DS) provides a model for studying important aspects of Alzheimer disease (AD). Chromosome 21 contains several genes that have been implicated in neurodegenerative mechanisms. These include Cu/Zn superoxide dismutase (SOD-1), Ets-2 transcription factors, Down Syndrome Critical Region 1 (DSCR1) stress-inducible factor, and the amyloid precursor protein (APP). The accumulation of Aβ plaques is Read More

Historical progress in medicine can be charted along the lines of technical innovations that have visualized the invisible. One hundred years ago, Alois Alzheimer exploited newly developed histological stains to visualize his eponymonous disease in dead tissue under the microscope. Now, as we are entering the second century of Alzheimer's disease research, technical innovation has endowed us with a range of in vivo imaging te Read More

The therapeutic use of enzyme inhibitors in treatment of neurodegenerative diseases has its origin in the anti Parkinson action of the selective monoamine oxidase (MAO) B inhibitor, l-deprenyl (selegiline ), a failed anti depressant in 1975. This led to further development of MAO- A and B, catechol-O-methyltansferase and cholinestrerase inhibitors as anti Parkinson and Alzheimer drugs. One of the main reasons for the cog Read More