After extensive development work, the Quantitative Morphometry Laboratory, Oregon Health Sciences University has reached the first level of functional performance of a newly assembled Image Analysis system capable of measuring neuritic plaque, neurofibrillary tangle, and amyloid burden within serially sectioned cerebral samples. Pilot studies recently completed have quantified plaque numbers form both hippocampal and neocortical samples of different brains, comparing manually obtained results by 3 independent observers, and matching these ranking orders with the data generated on the same samples through the Image Analysis system. This approach will be used to perfect a method for quantification of nerve cell numbers, completing all hardware and software modifications. This Image Analysis approach to quantitative neuropathological histomorphometry enables a more thorough sampling of large portions of gray matter during much shorter time, with the enhanced precision of computer-driven programs. The survey of hippocampal formation published earlier (Ball et al, 1988) automated observer analysis. this procedure required 3 months' technician's time per case. Most other quantitative sampling approaches actually analyze less than 0.1% of the total gyral gray matter. Our newly developed methodology will dramatically increase the rate of data acquisition, enabling surveys of up to 10% of actual, regional tissue volume in only a few days, with dramatically enhanced precision and reproducibility. In this fashion definitive correlations can be compared between neurological, psychological, and neuroimaging measurements and the true histopathological, severity of involvement in each lobe, from brains of both Alzheimer patients and age-matched normative controls.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
3P01AG003991-18S2
Application #
6500969
Study Section
Project Start
2001-09-30
Project End
2001-12-31
Budget Start
Budget End
Support Year
18
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Washington University
Department
Type
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Maxwell, Taylor J; Corcoran, Chris; Del-Aguila, Jorge L et al. (2018) Genome-wide association study for variants that modulate relationships between cerebrospinal fluid amyloid-beta 42, tau, and p-tau levels. Alzheimers Res Ther 10:86
Cruchaga, Carlos; Del-Aguila, Jorge L; Saef, Benjamin et al. (2018) Polygenic risk score of sporadic late-onset Alzheimer's disease reveals a shared architecture with the familial and early-onset forms. Alzheimers Dement 14:205-214
Brainstorm Consortium (see original citation for additional authors) (2018) Analysis of shared heritability in common disorders of the brain. Science 360:
Kinnunen, Kirsi M; Cash, David M; Poole, Teresa et al. (2018) Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial magnetic resonance imaging study. Alzheimers Dement 14:43-53
Ibanez, Laura; Dube, Umber; Davis, Albert A et al. (2018) Pleiotropic Effects of Variants in Dementia Genes in Parkinson Disease. Front Neurosci 12:230
Schultz, Stephanie A; Gordon, Brian A; Mishra, Shruti et al. (2018) Widespread distribution of tauopathy in preclinical Alzheimer's disease. Neurobiol Aging 72:177-185
Broce, Iris; Karch, Celeste M; Wen, Natalie et al. (2018) Correction: Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies. PLoS Med 15:e1002504
Javaherian, Kavon; Newman, Brianne M; Weng, Hua et al. (2018) Examining the Complicated Relationship Between Depressive Symptoms and Cognitive Impairment in Preclinical Alzheimer Disease. Alzheimer Dis Assoc Disord :
Liao, Fan; Li, Aimin; Xiong, Monica et al. (2018) Targeting of nonlipidated, aggregated apoE with antibodies inhibits amyloid accumulation. J Clin Invest 128:2144-2155
Jansen, Willemijn J; Ossenkoppele, Rik; Tijms, Betty M et al. (2018) Association of Cerebral Amyloid-? Aggregation With Cognitive Functioning in Persons Without Dementia. JAMA Psychiatry 75:84-95

Showing the most recent 10 out of 911 publications