Topics

Dominantly Inherited Alzheimer Network (DIAN)

2014-08-27 03:23:22 | BioPortfolio

Summary

The purpose of this study is to identify potential biomarkers that may predict the development of Alzheimer's disease in people who carry an Alzheimer's mutation.

Description

Dominantly inherited Alzheimer's disease (AD) represents less than 1% of all cases of AD and is an important model for study because the responsible mutations have known biochemical consequences that are believed to underlie the pathological basis of the disorder. Three major hypotheses will be tested:

- First, that there is a period of preclinical (presymptomatic) AD in individuals who are destined to develop early-onset dementia (gene carriers) that can be detected by changes in biological fluids and in neuroimaging correlates in comparison with individuals who will not develop early-onset dementia (non-carriers).

- Second, because all identified causative mutations for AD affect the normal processing of amyloid precursor protein (APP) and increase brain levels of amyloid-beta 42 (Aβ42), the sequence of preclinical changes initially will involve Aβ42 (production and clearance; reduced levels in cerebrospinal fluid [CSF]), followed by evidence for cerebral deposition of Aβ42 (amyloid imaging), followed by cerebral metabolic activity (functional imaging), and finally by regional atrophy (structural imaging).

- Finally, that the phenotype of symptomatic early-onset familial AD, including its clinical course, is similar to that of late-onset "sporadic" AD.

The following specific aims will be used to test these hypotheses:

1. Establish an international, multicenter registry of individuals (mutation carriers and non-carriers; pre-symptomatic and symptomatic) who are biological adult children of a parent with a known causative mutation for AD in the APP, PSEN1, or PSEN2 genes in which the individuals are evaluated in a uniform manner at entry and longitudinally thereafter with standardized instruments.

2. In pre-symptomatic individuals, compare mutation carriers and non-carriers to determine the order in which changes in clinical, cognitive, neuroimaging, and biomarker indicators of AD occur prior to the occurrence of dementia.

3. In symptomatic individuals, compare the clinical and neuropathological phenotypes of autosomal dominant AD to those of late-onset "sporadic" AD (using the data sets established by ADNI and by NACC).

4. Maintain the DIAN Central Archive, an integrated database incorporating all information obtained from individuals in the registry to permit analyses within, between, and among the various data domains and also to disseminate the data to qualified investigators in a user-friendly manner.

5. All DIAN participants who wish to know their mutation status will have the costs of genetic counseling and clinical mutation testing paid for by the grant. The clinical genetic counseling and testing is provided as an optional participant benefit and is not part of the DIAN research design.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Conditions

Alzheimer's Disease

Location

University of California, Los Angeles
Los Angeles
California
United States
90095

Status

Recruiting

Source

National Institute on Aging (NIA)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:23:22-0400

Clinical Trials [1155 Associated Clinical Trials listed on BioPortfolio]

Imaging Inflammation in Alzheimer's Disease With 11C-ER176

This study is being done to learn about inflammation in the brain of those with Alzheimer's disease (AD). The purpose of this study is to determine if 11C-ER176 is able to accurately measu...

Blood Biomarker of Alzheimer's Disease (AD)

Currently, no cures or disease modifying therapies exist for Alzheimer's disease (AD). This is partially due to the inability to detect the disease before it has progressed to a stage wher...

Biodistribution of [11C]PIB in Patients With Risk Factors for Alzheimer's Disease

Participants enrolled in the Alzheimer's Disease Clinical Core at Wake Forest School of Medicine will be invited to take part in this study. The purpose of this study is to identify and me...

Effect of Choline Alphoscerate on Cognitive Function in Alzheimer's Dementia

This study will evaluate the performance of Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) in patients with Alzheimer's disease (AD).

Antigonadotropin-Leuprolide in Alzheimer's Disease Drug INvestigation (ALADDIN) VP 104 Study

ALADDIN is a research study to investigate the safety and effectiveness of leuprolide (a hormone drug) to improve the cognitive function and slow the progression of Alzheimer's disease (AD...

PubMed Articles [15184 Associated PubMed Articles listed on BioPortfolio]

Interaction between APOE4 and herpes simplex virus type 1 in Alzheimer's disease.

Numerous results suggest the implication of infectious agents in the onset of Alzheimer's disease (AD).

miR-16-5p and miR-19b-3p prevent amyloid β-induced injury by targeting BACE1 in SH-SY5Y cells.

Alzheimer's disease is the most common neurodegenerative disease, characterized by accumulation of amyloid β peptides. MicroRNAs have been identified as significant regulators and therapeutic targets...

Tau Aggregation Correlates with Amyloid Deposition in Both Mild Cognitive Impairment and Alzheimer's Disease Subjects.

Amyloid plaque and tau-containing neurofibrillary tangles are important features of Alzheimer's disease (AD). However, the relationship between these processes is still debated.

A pilot study of exenatide actions in Alzheimer's disease.

Strong preclinical evidence suggests that exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist used for treating type 2 diabetes, is neuroprotective and disease- modifying in Alzheimer's dise...

"Like He's a Kid": Relationality, Family Caregiving, and Alzheimer's Disease.

Spousal caregivers draw upon understandings of shifting relationality to maintain a familial understanding of their spouse with Alzheimer's disease. Working through what it means to think of an adult ...

Medical and Biotech [MESH] Definitions

Abnormal structures located chiefly in distal dendrites and, along with NEUROFIBRILLARY TANGLES and SENILE PLAQUES, constitute the three morphological hallmarks of ALZHEIMER DISEASE. Neuropil threads are made up of straight and paired helical filaments which consist of abnormally phosphorylated microtubule-associated tau proteins. It has been suggested that the threads have a major role in the cognitive impairment seen in Alzheimer disease.

Vaccines or candidate vaccines used to prevent or treat ALZHEIMER DISEASE.

A progressive form of dementia characterized by the global loss of language abilities and initial preservation of other cognitive functions. Fluent and nonfluent subtypes have been described. Eventually a pattern of global cognitive dysfunction, similar to ALZHEIMER DISEASE, emerges. Pathologically, there are no Alzheimer or PICK DISEASE like changes, however, spongiform changes of cortical layers II and III are present in the TEMPORAL LOBE and FRONTAL LOBE. (From Brain 1998 Jan;121(Pt 1):115-26)

A carbamate-derived reversible CHOLINESTERASE INHIBITOR that is selective for the CENTRAL NERVOUS SYSTEM and is used for the treatment of DEMENTIA in ALZHEIMER DISEASE and PARKINSON DISEASE.

A biochemical phenomenon in which misfolded proteins aggregate either intra- or extracellularly. Triggered by factors such as MUTATION, POST-TRANSLATIONAL MODIFICATIONS, and environmental stress, it is generally associated with ALZHEIMER DISEASE; PARKINSON DISEASE; HUNTINGTON DISEASE; and TYPE 2 DIABETES MELLITUS.

More From BioPortfolio on "Dominantly Inherited Alzheimer Network (DIAN)"

Quick Search

Searches Linking to this Trial