Biomarker Modeling of Alzheimer's Disease

By Clifford R. Jack Jr., D. Holtzman. Neuron, 2013

976 citations recorded by the source corpus.

Alzheimer's disease (AD) is a slowly progressing disorder in which pathophysiological abnormalities, detectable in vivo by biomarkers, precede overt clinical symptoms by many years to decades. Five AD biomarkers are sufficiently validated to have been incorporated into clinical diagnostic criteria and commonly used in therapeutic trials. Current AD biomarkers fall into 2 categories: biomarkers of amyloid-β plaques and of tau-related neurodegeneration. Three of the 5 are imaging measures and two are cerebrospinal fluid analytes. AD biomarkers do not evolve in an identical manner but rather in a sequential but temporally overlapping manner. Models of the temporal evolution of AD biomarkers can take the form of plots of biomarker severity (degree of abnormality) vs. time. In this review we discuss several time-dependent models of AD which take into consideration varying age of onset (early vs. late) and the influence of aging and co-occurring brain pathologies that commonly arise in the elderly.

Subfields: Molecular Biology, Physiology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/0cab9261741de8983192002e29561c3109e6ccf4

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. D. Holtzman
2. J. Long
3. D. Selkoe
4. Kaj Blennow
5. John Hardy
6. William J. Jagust
7. Clifford R. Jack Jr.
8. Harald Hampel

In Physiology

1. D. Holtzman
2. Kaj Blennow
3. Clifford R. Jack Jr.
4. J. Long
5. Reisa A. Sperling
6. John Hardy
7. D. Selkoe
8. Ronald C. Petersen

In Psychiatry and Mental health

1. Clifford R. Jack Jr.
2. J. Long
3. D. Holtzman
4. Kaj Blennow
5. Ronald C. Petersen
6. Reisa A. Sperling
7. John Hardy
8. William J. Jagust

Citations in the corpus

• The amyloid hypothesis of Alzheimer's disease at 25 years (2016, background): “Overall, brain imaging and CSF biomarker studies in humans suggest that the sequence of AD pathogenic steps currently measurable in vivo broadly follows the schema proposed by Jack and colleagues (Jack & Holtzman, 2013; Jack et al, 2013; Fig 3).”
• A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers (2016, background): “More abnormal values in all 3 of these biomarkers are strongly associated with worse cognitive symptoms throughout the clinical spectrum, which is not the case for amyloid biomarkers.(15) The topography of hypometabolism and atrophy maps well onto the expression of clinical symptoms, which is not th”
• Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria (2016, background): “There are circumstances where pathologic tau hyperphosphorylation and the related neurodegeneration process begin ahead of brain amyloidopathy (tau first) [12,13].”
• Fifty Shades of Brain: A Review on the Mechanical Testing and Modeling of Brain Tissue (2019, methodology): “When integrated across the brain, the concentration profiles result in biomarker curves that display a striking similarity with the sigmoid shape and qualitative timeline of clinical biomarker models [82].”
• Oxidative Stress, Synaptic Dysfunction, and Alzheimer’s Disease (2017, background): “While excessive production of A peptides is observed early in patients that develop AD and is essential for AD pathology [20], it is not sufficient.”
• Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019, positive): “, 2019), characterized by early deposition of Aβ in the precuneus and other cortical regions comprising the default mode network, followed sequentially by regional cortical hypometabolism, accumulation of tau pathology, hippocampal volume loss, and onset of symptomatic cognitive impairment (Figure 1”