Molecular, Structural, and Functional Characterization of Alzheimer's Disease: Evidence for a Relationship between Default Activity, Amyloid, and Memory

By Randy L. Buckner, Abraham Z. Snyder, Benjamin J. Shannon, Gina N. LaRossa, R. Sachs, Anthony F. Fotenos, Yvette I. Sheline, William E. Klunk, Chester A. Mathis, John C. Morris and 1 more. Journal of Neuroscience, 2005

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Alzheimer's disease (AD) and antecedent factors associated with AD were explored using amyloid imaging and unbiased measures of longitudinal atrophy in combination with reanalysis of previous metabolic and functional studies. In total, data from 764 participants were compared across five in vivo imaging methods. Convergence of effects was seen in posterior cortical regions, including posterior cingulate, retrosplenial, and lateral parietal cortex. These regions were active in default states in young adults and also showed amyloid deposition in older adults with AD. At early stages of AD progression, prominent atrophy and metabolic abnormalities emerged in these posterior cortical regions; atrophy in medial temporal regions was also observed. Event-related functional magnetic resonance imaging studies further revealed that these cortical regions are active during successful memory retrieval in young adults. One possibility is that lifetime cerebral metabolism associated with regionally specific default activity predisposes cortical regions to AD-related changes, including amyloid deposition, metabolic disruption, and atrophy. These cortical regions may be part of a network with the medial temporal lobe whose disruption contributes to memory impairment.

Subfields: Cognitive Neuroscience, Physiology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/84488c97e912a8a59b40b3f1b870bdfe738d424c

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Citations in the corpus

What is normal in normal aging? Effects of Aging, Amyloid and Alzheimer’s Disease on the Cerebral Cortex and the Hippocampus (2014, background): “, 2003), and the high overlap between DMN and areas of Ab deposition and PET-FDG hypo metabolism (Buckner et al., 2005).”
Predicting regional neurodegeneration from the healthy brain functional connectome. (2012, background): “Although previous studies have demonstrated the similarity between single seed-based healthy ICNs and diseaserelated atrophy (Buckner et al., 2005; Seeley et al., 2009), the present study used a comprehensive, high-dimensional network mapping strategy to seek out those regions with connectivity…”
One year brain atrophy evident in healthy aging (2009, background): “4% in large areas of the brain, including the frontal cortex (Buckner et al., 2005).”
Activity Dependent Degeneration Explains Hub Vulnerability in Alzheimer's Disease (2012, background): “As can be judged from table 1, many Default Mode Network (DMN)-related regions possess a high degree of connectivity and activity.”
Advances and Pitfalls in the Analysis and Interpretation of Resting-State FMRI Data (2010, positive): “…also provide complementary information to that gained from other imaging modalities and structural connectivity metrics, helping to further map and quantify the neural substrates of systems-level function and dysfunction (e.g., Buckner et al., 2005; Greicius et al., 2009; Seeley et al., 2009).”
Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer's disease (2009, neutral): “, 2007) or automated whole-brain approaches (Scahill et al., 2002; Buckner et al., 2005; Dickerson et al., 2009) to identify MCI and Alzheimer’s disease individuals.”
Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer’s Disease (2009, background): “The identification of cortical hubs may explain why certain regions of cortex show disproportionately high levels of metabolism (Minoshima et al., 1997) and, as a result, preferential vulnerability to AD pathology (Buckner et al., 2005, 2008).”
Trafficking and proteolytic processing of APP. (2012, background): “Moreover, regions of the brain that develop the highest levels of Ab plaques, including the frontal and parietal lobes and posterior cingulate cortex, exhibit the highest baseline metabolic activity in the so-called “default network” (Gusnard et al. 2001; Raichle et al. 2001; Buckner et al. 2005).”
Competition between functional brain networks mediates behavioral variability (2008, background): “, 2006), Alzheimer’s disease (Buckner et al., 2005; Greicius et al., 2004; Wang et al., 2006) and schizophrenia (Liang et al.”
Brain imaging in Alzheimer disease. (2012, background): “2; Klunk et al. 2004; Buckner et al. 2005, 2009; Sperling et al. 2009).”
Cingulate-precuneus interactions: a new locus of dysfunction in adult attention-deficit/hyperactivity disorder. (2008, background): “By definition, default-mode network activity can be detected during resting state scans, and abnormalities in this network have been reported in ADHD (17,18), Alzheimer’s disease (19,20), autism (21), schizophrenia (22), and depression (23).”
The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals (2008, methodology): “Although previous data suggest that regional deposition of amyloid overlaps in part with areas of cortical atrophy in AD (Buckner et al. 2005), the question of whether it is possible to detect subtle regional cortical thinning in older individuals with brain amyloid has never been investigated.”
Does the brain have a baseline? Why we should be resisting a rest (2007, background): “It is possible that this regional modal level of metabolic activity might also have implications for regional sensitivity to certain kinds of pathology or insult (Raichle et al., 2001; Buckner et al., 2005).”