CD33 Alzheimer’s disease locus: Altered monocyte function and amyloid biology

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

In our functional dissection of the CD33 Alzheimer’s disease susceptibility locus, we find that the rs3865444 ^C risk allele is associated with greater cell surface expression of CD33 in monocytes ( t ₅₀ = 10.06, pjoint=1.3×10–13) of young and older individuals. It is also associated with (1) diminished internalization of Aβ42) (2) accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging and (3), increased numbers of activated human microglia.

Related collections

Most cited references 25

Record: found
Abstract: found
Article: not found

Development and validation of a geriatric depression screening scale: a preliminary report.

J Yesavage, T. Brink, T Rose … (1982)

A new Geriatric Depression Scale (GDS) designed specifically for rating depression in the elderly was tested for reliability and validity and compared with the Hamilton Rating Scale for Depression (HRS-D) and the Zung Self-Rating Depression Scale (SDS). In constructing the GDS a 100-item questionnaire was administered to normal and severely depressed subjects. The 30 questions most highly correlated with the total scores were then selected and readministered to new groups of elderly subjects. These subjects were classified as normal, mildly depressed or severely depressed on the basis of Research Diagnostic Criteria (RDC) for depression. The GDS, HRS-D and SDS were all found to be internally consistent measures, and each of the scales was correlated with the subject's number of RDC symptoms. However, the GDS and the HRS-D were significantly better correlated with RDC symptoms than was the SDS. The authors suggest that the GDS represents a reliable and valid self-rating depression screening scale for elderly populations.

0 comments Cited 958 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Graphical analysis of reversible radioligand binding from time-activity measurements applied to [N-11C-methyl]-(-)-cocaine PET studies in human subjects.

J. Logan, J Fowler, N D Volkow … (1990)

A graphical method of analysis applicable to ligands that bind reversibly to receptors or enzymes requiring the simultaneous measurement of plasma and tissue radioactivities for multiple times after the injection of a radiolabeled tracer is presented. It is shown that there is a time t after which a plot of integral of t0ROI(t')dt'/ROI(t) versus integral of t0Cp(t')dt'/ROI(t) (where ROI and Cp are functions of time describing the variation of tissue radioactivity and plasma radioactivity, respectively) is linear with a slope that corresponds to the steady-state space of the ligand plus the plasma volume,.Vp. For a two-compartment model, the slope is given by lambda + Vp, where lambda is the partition coefficient and the intercept is -1/[kappa 2(1 + Vp/lambda)]. For a three-compartment model, the slope is lambda(1 + Bmax/Kd) + Vp and the intercept is -[1 + Bmax/Kd)/k2 + [koff(1 + Kd/Bmax)]-1) [1 + Vp/lambda(1 + Bmax/Kd)]-1 (where Bmax represents the concentration of ligand binding sites and Kd the equilibrium dissociation constant of the ligand-binding site complex, koff (k4) the ligand-binding site dissociation constant, and k2 is the transfer constant from tissue to plasma). This graphical method provides the ratio Bmax/Kd from the slope for comparison with in vitro measures of the same parameter. It also provides an easy, rapid method for comparison of the reproducibility of repeated measures in a single subject, for longitudinal or drug intervention protocols, or for comparing experimental results between subjects. Although the linearity of this plot holds when ROI/Cp is constant, it can be shown that, for many systems, linearity is effectively reached some time before this. This analysis has been applied to data from [N-methyl-11C]-(-)-cocaine ([11C]cocaine) studies in normal human volunteers and the results are compared to the standard nonlinear least-squares analysis. The calculated value of Bmax/Kd for the high-affinity binding site for cocaine is 0.62 +/- 0.20, in agreement with literature values.

0 comments Cited 251 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Disruption of functional connectivity in clinically normal older adults harboring amyloid burden.

A. Mehta, Ronald Van Ree, Andrew Frederick Johnson … (2009)

Amyloid deposition is present in 20-50% of nondemented older adults yet the functional consequences remain unclear. The current study found that amyloid accumulation is correlated with functional disruption of the default network as measured by intrinsic activity correlations. Clinically normal participants (n = 38, aged 60-88 years) were characterized using (11)C-labeled Pittsburgh Compound B positron emission tomography imaging to estimate fibrillar amyloid burden and, separately, underwent functional magnetic resonance imaging (fMRI). The integrity of the default network was estimated by correlating rest-state fMRI time courses extracted from a priori regions including the posterior cingulate, lateral parietal, and medial prefrontal cortices. Clinically normal participants with high amyloid burden displayed significantly reduced functional correlations within the default network relative to participants with low amyloid burden. These reductions were also observed when amyloid burden was treated as a continuous, rather than a dichotomous, measure and when controlling for age and structural atrophy. Whole-brain analyses initiated by seeding the posterior cingulate cortex, a region of high amyloid burden in Alzheimer's disease, revealed significant disruption in the default network including functional disconnection of the hippocampal formation.

0 comments Cited 167 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-journal-id): 9809671

Journal ID (pubmed-jr-id): 21092

Journal ID (nlm-ta): Nat Neurosci

Journal ID (iso-abbrev): Nat. Neurosci.

Title: Nature neuroscience

ISSN (Print): 1097-6256

ISSN (Electronic): 1546-1726

Publication date Nihms-submitted: 6 June 2013

Publication date (Electronic): 23 May 2013

Publication date (Print): July 2013

Publication date PMC-release: 23 November 2013

Volume: 16

Issue: 7

Pages: 848-850

Affiliations

[1 ]Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA

[2 ]Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women’s Hospital, 77 Avenue Louis Pasteur, NRB168, Boston, MA 02115

[3 ]Harvard Medical School, Boston, MA 02115

[4 ]Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, MA 02142

[5 ]Rush Alzheimer’s Disease Center, Rush University Medical Center, 600 S Paulina St., Chicago, IL 60612

[6 ]Rush Institute for Healthy Aging, Rush University Medical Center,1645 W. Jackson Blvd., Chicago 60612

[8 ]Department of Neurology, Center for Alzheimer’s Research and Treatment, Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, MA 02115, USA

[9 ]Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

[10 ]The Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA

Author notes

Correspondence: Philip L. De Jager, MD, PhD, Program in Translational NeuroPsychiatric Genomics, Departments of Neurology& Psychiatry, Brigham and, Women’s Hospital, 77 Avenue Louis Pasteur, NRB, 168C, Boston, MA 02115, Phone: 617 525-4529, Fax:, 617 525-5333, pdejager@ 123456rics.bwh.harvard.edu

[7]

Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.ucla.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.ucla.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

Article

Manuscript ID: NIHMS481627

DOI: 10.1038/nn.3435

PMC ID: 3703870

PubMed ID: 23708142

SO-VID: 27e56eba-e5d3-44d6-b0d9-f4f3223f5334

License:

Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms