ApoE-4 and Age at Onset of Alzheimer's Disease

Blacker, Deborah; Haines, Jonathan L.; Rodes, Linda; Terwedow, Henry; Go, Rodney C.P.; Harrell, Lindy E.; Perry, Rodney T.; Bassett, Susan Spear; Chase, Gary A.; Meyers, David J.; Albert, Marilyn; Re, Tanzi

doi:10.1212/wnl.48.1.139

Cited by 446 publications

(315 citation statements)

References 17 publications

Supporting

Mentioning

280

Contrasting

Unclassified

Order By: Relevance

“…However, Li et al [14,40] argued that the age-atonset of disease is equally important because the "regulation of onset could make it possible to delay onset beyond an individual's normal life span." Indeed, allelic variation in APOE profoundly affects risk by lowering the age-at-onset of AD between three to five years with each copy of the ε4 variant [6,8,9]. The likelihood that variants in other genes could have similar effects on the age-at-onset was strengthened by a study finding that as many as four additional loci contribute to the variance in age-at-onset of LOAD [12].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Age-at-onset linkage analysis in Caribbean Hispanics with familial late-onset Alzheimer’s disease

et al. 2007

View full text Add to dashboard Cite

The aim of the study was to identify chromosomal regions containing putative genetic variants influencing age-at-onset in familial late-onset Alzheimer's disease. Data from a genome-wide scan that included genotyping of APOE was analyzed in 1,161 individuals from 209 families of Caribbean Hispanic ancestry with a mean age-at-onset of 73.3 years multiply affected by late-onset Alzheimer's disease. Two-point and multipoint analyses were conducted using variance component methods from 376 microsatellite markers with an average inter-marker distance of 9.3 cM. Family-based test of association were also conducted for the same set of markers. Age-at-onset of symptoms among affected individuals was used as the quantitative trait. Our results showed that the presence of APOE-ε4 lowered the age-at-onset by three years. Using linkage analysis strategy, the highest LOD scores were obtained using a conservative definition of LOAD at 5q15 (LOD 3.1) 17q25.1 (LOD=2.94) and 14q32.12 (LOD=2.36) and 7q36.3 (LOD=2.29) in covariate adjusted models that included APOE-ε4. Both linkage and family-based association identified 17p13 as a candidate region. In addition, family-based association analysis showed markers at 12q13 (p=0.00002), 13q (p=0.00043) and 14q23 (p=0.00046) to be significantly associated with age at onset. The current study supports the hypothesis that there are additional genetic loci that could influence age-at-onset of late onset

show abstract

Section: Discussionmentioning

confidence: 99%

“…Variants in APOE provide an example. The number of APOE-ε4 alleles consistently influences age-at-onset of LOAD [6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Age-at-onset linkage analysis in Caribbean Hispanics with familial late-onset Alzheimer’s disease

et al. 2007

View full text Add to dashboard Cite

show abstract

“…The recognised genetic factors include mutations of the genes encoding the amyloid precursor protein [14] and presenilin 1 and 2 [16,31], which are responsible for a small proportion of familial and usually early-onset AD cases. A fourth gene encoding apolipoprotein E (APOE) is also implicated in the risk of developing the disease [4,23,29,36]. However, although APOE-⑀4 is a major risk factor for AD, it is neither necessary nor sufficient for the development of the disease and the presence of other genetic or acquired factors has been postulated.…”

Section: Introductionmentioning

confidence: 99%

The hemochromatosis gene affects the age of onset of sporadic Alzheimer’s disease

Sampietro

Caputo

Casatta

et al. 2001

Neurobiology of Aging

104

View full text Add to dashboard Cite

NEUROBIOL AGING. In the present study we analysed the genotype of HFE, the gene involved in hemochromatosis, in 107 patients with sporadic late-onset AD and in 99 age-matched non-demented controls. We observed that patients carrying the mutant HFE-H63D allele had a mean age at onset of 71.7 Ϯ 6.0 years versus 76.6 Ϯ 5.8 years of those who were homozygous for the wild-type allele (p ϭ 0.001). The frequency of the HFE-H63D mutation was highest (0.22) in the patients aged Ͻ70 years at the time of disease onset, whereas it was 0.12 in those with disease onset at an age of 70 -80 years, and 0.04 in those aged more than 80 years. The APOE genotype did not significantly modify the effect of HFE on age at onset. We conclude that mild disturbances of iron homeostasis associated with a common genetic determinant may interact with other pathogenic mechanisms involved in AD. HFE mutations may anticipate AD clinical presentation in susceptible individuals.

show abstract

“…43 The ε4 allele is also associated with decreased age of the AD onset and with an increased conversion from MCI to AD. 44,45 On the contrary, inheritance of the ε2 allele appears to protect against AD pathogenesis. 46 The mechanism by which apoE-ε4 promotes the disease is still an argument of research.…”

Section: ■ Etiology Of Admentioning

confidence: 99%

Alzheimer’s Disease: Pathophysiology and Applications of Magnetic Nanoparticles as MRI Theranostic Agents

Amiri

Saeidi²,

Borhani³

et al. 2013

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Alzheimer's disease (AD) is the most common form of dementia. During the recent decade, nanotechnology has been widely considered, as a promising tool, for theranosis (diagnosis and therapy) of AD. Here we first discuss pathophysiology and characteristics of AD with a focus on the amyloid cascade hypothesis. Then magnetic nanoparticles (MNPs) and recent works on their applications in AD, focusing on the superparamagnetic iron oxide nanoparticles (SPIONs), are reviewed. Furthermore, the amyloid−nanoparticle interaction is highlighted, with the scope to be highly considered by the scientists aiming for diagnostics and/or treatment of AD employing nanoparticles. Furthermore, recent findings on the "ignored" parameters (e.g., effect of protein "corona" at the surface of nanoparticles on amyloid-β (Aβ) fibrillation process) are discussed. KEYWORDS: Magnetic resonance imaging, SPION, amyloid-β, nanomedicine, nanotechnology A lzheimer's disease (AD) is named after Alois Alzheimer, who described the first case in a 55 year old female patient (i.e., Auguste Deter) in 1906. The description of Auguste's pathology was featured by lifelong deteriorating memory, speaking, physical, and social abilities. After her death, the autopsy revealed uniform brain atrophy, atherosclerosis changes in larger cerebral vessels, neuronal loss, and numerous small foci perceivable even without staining distributed over the entire cortex. It took over 70 years to reveal that those foci consist of aggregates of extracellular loads of small peptides called amyloid-β (Aβ), that are considered today one of the hallmarks of the disease. 1 AD is characterized by progressive deterioration of cognitive function, most commonly of memory, that increasingly interferes with patients' daily activities leading to loss of independency (for details, see http://www.alz.org/downloads/ facts_figures_2012.pdf). To date, no precise treatments have been clinically proven to avoid or prevent the progression of AD. Several different pharmacological agents can only ameliorate or provide temporary alleviation of the symptoms. 2 In this review, we introduce clinical aspects and characteristics of AD with a focus on the amyloid cascade hypothesis. Magnetic nanoparticles (MNPs), as promising theranosis tools, are introduced, and recent reports on the potential applications of superparamagnetic iron oxide nanoparticles (SPIONs) in AD are summarized. It is worthwhile to note that the SPIONs are known as promising theranosis candidates for AD, due to their biocompatibility, unique magnetic properties and multifunctional application capability. 3,4 The amyloid−nanoparticle interaction is highlighted, with the scope to be highly considered by the scientific community aiming for diagnostics and/or treatment of AD employing nanoparticles. Moreover, recent findings on the "ignored" parameters (e.g., the effect of protein "corona" at the surface of nanoparticles on Aβ fibrillation process) are discussed.

show abstract

ApoE-4 and Age at Onset of Alzheimer's Disease

Cited by 446 publications

References 17 publications

Age-at-onset linkage analysis in Caribbean Hispanics with familial late-onset Alzheimer’s disease

Age-at-onset linkage analysis in Caribbean Hispanics with familial late-onset Alzheimer’s disease

The hemochromatosis gene affects the age of onset of sporadic Alzheimer’s disease

Alzheimer’s Disease: Pathophysiology and Applications of Magnetic Nanoparticles as MRI Theranostic Agents

Contact Info

Product

Resources

About