TITLE

Neuronal LR11 Expression Does Not Differentiate between Clinically-Defined Alzheimer's Disease and Control Brains

AUTHOR(S)
Sager, Kristen L.; Wuu, Joanne; Herskowitz, Jeremy H.; Mufson, Elliott J.; Levey, Allan I.; Lah, James J.; Ginsberg, Stephen D.
PUB. DATE
August 2012
SOURCE
PLoS ONE;Aug2012, Vol. 7 Issue 8, Special section p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Because the pathological changes underlying this disease can begin decades prior to the onset of cognitive impairment, identifying the earliest events in the AD pathological cascade has critical implications for both the diagnosis and treatment of this disease. We previously reported that compared to autopsy confirmed healthy control brain, expression of LR11 (or SorLA) is markedly reduced in AD brain as well as in a subset of people with mild cognitive impairment (MCI), a prodromal clinical stage of AD. Recent studies of the LR11 gene SORL1 have suggested that the association between SORL1 single nucleotide polymorphisms (SNPs) and AD risk may not be universal. Therefore, we sought to confirm our earlier findings in a population chosen solely based on clinical criteria, as in most genetic studies. Quantitative immunohistochemistry was used to measure LR11 expression in 43 cases from the Religious Orders Study that were chosen based on a final pre-mortem clinical diagnosis of MCI, mild/moderate AD or no cognitive impairment (NCI). LR11 expression was highly variable in all three diagnostic groups, with no significant group differences. Low LR11 cases were identified using the lowest tertile of LR11 expression observed across all cases as a threshold. Contrary to previous reports, low LR11 expression was found in only 29% of AD cases. A similar proportion of both the MCI and NCI cases also displayed low LR11 expression. AD-associated lesions were present in the majority of cases regardless of diagnostic group, although we found no association between LR11 levels and pathological variables. These findings suggest that the relationship between LR11 expression and the development of AD may be more complicated than originally believed.
ACCESSION #
80433765

 

Related Articles

  • Apolipoprotein E Polymorphism in Alzheimer’s Disease: A Comparative Study of Two Research Populations from Spain and the United States. Lopez, Oscar L.; Lopez-Pousa, Secundino; Kamboh, M. Ilyas; Adroer, Rosa; Oliva, Rafael; Lozano-Gallego, Manuela; Becker, James T.; DeKosky, Steven T. // European Neurology;1998, Vol. 39 Issue 4, p229 

    We examined the distribution of the apolipoprotein E (APOE) polymorphism in two Caucasian populations of Alzheimer’s disease (AD) patients referred to dementia clinics; one in Gerona, Spain (66 AD patients, 49 controls), and the other in Pittsburgh, Pa., USA (209 AD patients, 58...

  • Insulin-Degrading Enzyme Haplotypes Affect Insulin Levels but Not Dementia Risk. Marlowe, Lauren; Peila, Rita; Benke, Kelly Suzanne; Hardy, John; White, Lon R.; Launer, Lenore J.; Myers, Amanda // Neurodegenerative Diseases;2006, Vol. 3 Issue 6, p320 

    Background: Insulin-degrading enzyme (IDE) polymorphism is hypothesized to regulate insulin levels as well as processes involved in neuronal compromise found in dementia. Methods: We examined the association of IDE haplotypes with dementia and insulin levels in a single well-characterized cohort...

  • Immunolocalization of an Amino-Terminal Fragment of Apolipoprotein E in the Pick's Disease Brain. Rohn, Troy T.; Day, Ryan J.; Catlin, Lindsey W.; Brown, Raquel J.; Rajic, Alexander J.; Poon, Wayne W. // PLoS ONE;Dec2013, Vol. 8 Issue 12, p1 

    Although the risk factor for apolipoprotein E (apoE) polymorphism in Alzheimer's disease (AD) has been well described, the role that apoE plays in other neurodegenerative diseases, including Pick's disease, is not well established. To examine a possible role of apoE in Pick's disease, an...

  • Polymorphisms in the LOC387715/ARMS2 Putative Gene and the Risk for Alzheimer’s Disease. Gatta, Luisa Benerini; Vitali, Massimiliano; Zanola, Alessandra; Venturelli, Eliana; Fenoglio, Chiara; Galimberti, Daniela; Scarpini, Elio; Finazzi, Dario // Dementia & Geriatric Cognitive Disorders;2008, Vol. 26 Issue 2, p169 

    Background: Age-related macular degeneration (ARMD) and Alzheimer’s disease (AD) are neurodegenerative disorders that share a high prevalence among elderly people, the extracellular deposition of β-amyloid and the involvement of genetic factors in their aetiology. Genetic linkage with...

  • Analysis of UBQLN1 Variants in a Polish Alzheimer’s Disease Patient: Control Series. Golan, Maciej P.; Melquist, Stacey; Safranow, Krzysztof; Styczyńska, Maria; Słowik, Agnieszka; Kobryś, Małgorzata; Żekanowski, Cesary; Barcikowska, Maria // Dementia & Geriatric Cognitive Disorders;2008, Vol. 25 Issue 4, p366 

    Late-onset Alzheimer’s disease (LOAD) is the most common neurodegenerative disorder, and has a complex etiology. Recently an intronic polymorphism in the ubiquilin 1 gene (UBQLN1) and a particular haplotype was reported to be associated with LOAD. We investigated whether variants in...

  • Do the Longevity Genes Prevent Dementia? Kennedy, Gary J. // Primary Psychiatry;Mar2010, Vol. 17 Issue 3, p20 

    The identification of genetic risk factors for the familial dementias has been a productive area of scientific study, but the clinical impact for the far more common sporadic dementias has been modest at best. As a result, interest in the characterization of biomedical and psychosocial...

  • Genetic association of an LBP-1c/CP2/LSF gene polymorphism with late onset Alzheimer's disease. Taylor, Alison E.; Yip, Agustin; Brayne, Carol; Easton, Douglas; Evans, John Grimley; Xuereb, John; Cairns, Nigel; Esiri, Margaret M.; Rubinsztein, David C. // Journal of Medical Genetics;Apr2001, Vol. 38 Issue 4, p232 

    Objectives--The only locus unequivocally associated with late onset Alzheimer's disease (AD) risk is APOE. However, this locus accounts for less than half the genetic variance. A recent study suggested that the A allele of the 3′UTR biallelic polymorphism in the LBP-1c/CP2/LSF gene was...

  • Interleukin-1α and -1β Promoter Polymorphisms in Taiwanese Patients with Dementia. Hsiu-Kuan Wang; Wen-Chuin Hsu; Hon-Chung Fung; Jun-Cheng Lin; Hai-Pei Hsu; Yih-Ru Wu; Yuying Hsu; Fen-Ju Hu; Guey-Jen Lee-Chen; Chiung-Mei Chen // Dementia & Geriatric Cognitive Disorders;2007, Vol. 24 Issue 2, p104 

    Background: Inflammatory events may contribute to the pathogenesis of dementia and interleukin-1 (IL-1) may exert both neurotoxic and neuroprotective effects. We investigated whether IL-1α –889 C/T and IL-1β –511 C/T promoter polymorphisms are associated with the risk of...

  • Presenilin Gene Predisposes to Late-Onset Degenerative but Not Vascular Dementia: A Comparative Study of PS1 and ApoE Genes in a North Indian Cohort. Pandey, Pratima; Pradhan, Sunil; Mittal, Balraj // Dementia & Geriatric Cognitive Disorders;2007, Vol. 24 Issue 3, p151 

    Background: Variation in the presenilin gene shifts the cleavage site of amyloid precursor protein producing an insoluble peptide Aβ42 (instead of Aβ40, which is soluble when produced in restricted amount), which is prone to aggregation in the brain in the form of amyloid plaques not only...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics