Alzheimer's-type neuropathology in the precuneus is not increased relative to other areas of neocortex across a range of cognitive impairment

Department of Pathology and Division of Neuropathology, University of Kentucky Medical Center, Sanders-Brown Center on Aging and Alzheimer's Disease Center, University of Kentucky, Lexington, KY 40536, USA.
Neuroscience Letters (Impact Factor: 2.03). 12/2008; 450(3):336-9. DOI: 10.1016/j.neulet.2008.11.006
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We studied Alzheimer's disease (AD) pathology in the precuneus and surrounding brain areas. Anatomically, the precuneus corresponds to the medial portion of human cerebral cortical Brodmann Area 7. This study utilized patients from the University of Kentucky Alzheimer's Disease Center autopsy cohort. Data from 47 brains were used comprising patients of differing antemortem cognitive impairment severities, each with longitudinal clinical data and extensive neuropathological data. We assessed whether the precuneus and surrounding areas are differentially vulnerable to AD-type pathological lesions (diffuse amyloid plaques, neuritic amyloid plaques, and neurofibrillary tangles). Eleven areas of brain were evaluated for each case: amygdala, hippocampal CA1, subiculum, entorhinal cortex, frontal cortex, superior and middle temporal gyri, inferior parietal lobule, occipital cortex, posterior cingulate gyrus, Brodmann Area 31, and the precuneus proper. Like other areas of neocortex, the precuneus demonstrated increased diffuse and neuritic amyloid plaques early in the evolution in AD, and increased neurofibrillary tangles late in AD. Correcting for the antemortem cognitive status of the patients, there was no evidence of an increase in the density of AD-type pathology in the precuneus or neighboring areas relative to other areas of cerebral neocortex. Our results are not consistent with the idea that the precuneus is involved in a special way with plaques or tangles relative to other areas of neocortex.

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Available from: Erin Abner, Aug 26, 2014
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    • "In addition, the PCG demonstrates a significant reduction of mitochondrial cytochrome C oxidase activity in young adults that carry the APOE ε4 allele [21]. The Pc and PCG have been associated with a higher burden of fibrillar Aβ in cognitively normal older individuals as determined by Pittsburgh compound B (PiB)-PET scans [22], although this observation has been disputed [23]. Lastly, the Pc and PCG are components of the default mode network (DMN), a complex system of functionally linked neurons active when the individual is disconnected from the outside environment. "
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    ABSTRACT: Defining the biochemical alterations that occur in the brain during "normal" aging is an important part of understanding the pathophysiology of neurodegenerative diseases and of distinguishing pathological conditions from aging-associated changes. Three groups were selected based on age and on having no evidence of neurological or significant neurodegenerative disease: 1) young adult individuals, average age 26 years (n = 9); 2) middle-aged subjects, average age 59 years (n = 5); 3) oldest-old individuals, average age 93 years (n = 6). Using ELISA and Western blotting methods, we quantified and compared the levels of several key molecules associated with neurodegenerative disease in the precuneus and posterior cingulate gyrus, two brain regions known to exhibit early imaging alterations during the course of Alzheimer's disease. Our experiments revealed that the bioindicators of emerging brain pathology remained steady or decreased with advancing age. One exception was S100B, which significantly increased with age. Along the process of aging, neurofibrillary tangle deposition increased, even in the absence of amyloid deposition, suggesting the presence of amyloid plaques is not obligatory for their development and that limited tangle density is a part of normal aging. Our study complements a previous assessment of neuropathology in oldest-old subjects, and within the limitations of the small number of individuals involved in the present investigation, it adds valuable information to the molecular and structural heterogeneity observed along the course of aging and dementia. This work underscores the need to examine through direct observation how the processes of amyloid deposition unfold or change prior to the earliest phases of dementia emergence.
    PLoS ONE 08/2014; 9(8):e105784. DOI:10.1371/journal.pone.0105784 · 3.23 Impact Factor
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    • "Structural and functional abnormalities of the IPL were observed in many neurological conditions, including Alzheimer's disease (Greene and Killiany, 2010; Hanggi et al., 2011; Nelson et al., 2009; Neufang et al., 2011; Xia and He, 2011; Zahn et al., 2005) and mild cognitive impairment (Chong and Sahadevan, 2005; Greene and Killiany, 2010; Hamalainen et al., 2007; Hanggi et al., 2011; Liang et al., 2012; Markesbery et al., 2006; Walker and Walker, 2005). For instance, Liang et al. (2012) showed that the AG connectivity with the DMN was significantly reduced in mild cognitive impairment. "
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    ABSTRACT: The human inferior parietal lobule (IPL) comprised the lateral bank of the intraparietal sulcus, angular gyrus and supramarginal gyrus, defined on the basis of anatomical landmarks and cytoarchitechtural organization of neurons. However, it is not clear whether the three areas represent functional subregions within the IPL. For instance, imaging studies frequently identified clusters of activities that cut across areal boundaries. Here, we used resting state functional magnetic resonance imaging (fMRI) data to examine how individual voxels within the IPL are best clustered according to their connectivity to the whole brain. The results identified a best estimate of 7 clusters which are hierarchically arranged as the anterior, middle, and posterior subregions. The anterior, middle, and posterior IPL are each significantly connected to the somatomotor areas, superior/middle/inferior frontal gyri, and regions of the default mode network. This functional segregation is supported by recent cytoarchitechtonics and tractography studies. IPL showed hemispheric differences in connectivity that accord with a predominantly left parietal role in tool use and language processing and a right parietal role in spatial attention and mathematical cognition. The functional clusters may also provide a more parsimonious and perhaps even accurate account of regional activations of the IPL during a variety of cognitive challenges, as reported in earlier fMRI studies.
    Brain Connectivity 12/2013; 4(1). DOI:10.1089/brain.2013.0191
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    • "Our use of an ROI analysis approach, as opposed to voxelwise analysis that may be more sensitive to localized changes within subregions of the precuneus, may also explain our findings. However, autopsy studies have not demonstrated a predilection for early amyloid plaque accumulation in the precuneus relative to other areas of the neocortex (Nelson et al. 2009), so further investigation of the relationship between amyloid and the precuneus is warranted. "
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    ABSTRACT: Neurofibrillary tangles (NFT) and amyloid plaques are hallmark neuropathological features of Alzheimer's disease (AD). There is some debate as to which neuropathological feature comes first in the disease process, with early autopsy studies suggesting that NFT develop first, and more recent neuroimaging studies supporting the early role of amyloid beta (Aβ) deposition. Cerebrospinal fluid (CSF) biomarkers of Aβ(42) and hyperphosphorylated tau (p-tau) have been shown to serve as in vivo proxy measures of amyloid plaques and NFT, respectively. The aim of this study was to examine the association between CSF biomarkers and rate of atrophy in the precuneus and hippocampus. These regions were selected because the precuneus appears to be affected early and severely by Aβ deposition, and the hippocampus similarly by NFT pathology. We predicted (1) baseline Aβ(42) would be related to accelerated rate of cortical thinning in the precuneus and volume loss in the hippocampus, with the latter relationship expected to be weaker, (2) baseline p-tau(181p) would be related to accelerated rate of hippocampal atrophy and cortical thinning in the precuneus, with the latter relationship expected to be weaker. Using all ADNI cohorts, we fitted separate linear mixed-effects models for changes in hippocampus and precuneus longitudinal outcome measures with baseline CSF biomarkers modeled as predictors. Results partially supported our hypotheses: Both baseline p-tau(181p) and Aβ(42) were associated with hippocampal atrophy over time. Neither p-tau(181p) nor Aβ(42) were significantly related to cortical thinning in the precuneus over time. However, follow-up analyses demonstrated that having abnormal levels of both Aβ(42) and p-tau(181p) was associated with an accelerated rate of atrophy in both the hippocampus and precuneus. Results support early effects of Aβ in the Alzheimer's disease process, which are less apparent than and perhaps dependent on p-tau effects as the disease progresses. However, amyloid deposition alone may be insufficient for emergence of significant morphometric changes and clinical symptoms.
    Brain Imaging and Behavior 05/2012; 6(4). DOI:10.1007/s11682-012-9171-6 · 4.60 Impact Factor
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