scholarly journals Association of APOE ɛ4 and Plasma p-tau181 with Preclinical Alzheimer’s Disease and Longitudinal Change in Hippocampus Function

2021 ◽  
pp. 1-12
Author(s):  
Alireza Salami ◽  
Rolf Adolfsson ◽  
Micael Andersson ◽  
Kaj Blennow ◽  
Anders Lundquist ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medial Temporal Lobe ◽  
Population Based ◽  
Longitudinal Change ◽  
Memory Encoding ◽  
Population Based Study ◽  
Functional Changes ◽  
Preclinical Ad ◽  
E4 Allele

Background: The Apolipoprotein E (APOE) ɛ4 allele has been linked to increased tau phosphorylation and tangle formation. APOE ɛ4 carriers with elevated tau might be at the higher risk for AD progression. Previous studies showed that tau pathology begins early in areas of the medial temporal lobe. Similarly, APOE ɛ4 carriers showed altered hippocampal functional integrity. However, it remains unknown whether elevated tau accumulation on hippocampal functional changes would be more pronounced for APOE ɛ4 carriers. Objective: We related ɛ4 carriage to levels of plasma phosphorylated tau (p-tau181) up to 15 years prior to AD onset. Furthermore, elevated p-tau181 was explored in relation to longitudinal changes in hippocampal function and connectivity. Methods: Longitudinal population-based study. Plasma p-tau181 was analyzed in 142 clinically defined Alzheimer’s disease (AD) cases and 126 controls. The longitudinal analysis involved 87 non-demented individuals with two waves of plasma samples and three waves of functional magnetic resonance imaging during rest and memory encoding. Results: Increased p-tau181 was observed for both ɛ4 carriers and non-carriers close to AD, but exclusively for ɛ4 carriers in the early preclinical groups (7- and 13-years pre-AD). In ɛ4 carriers, longitudinal p-tau181 increase was paralleled by elevated local hippocampal connectivity at rest and subsequent reduction of hippocampus encoding-related activity. Conclusion: Our findings support an association of APOE ɛ4 and p-tau181 with preclinical AD and hippocampus functioning.

scholarly journals Apolipoprotein E4 allele in a population–based study of early–onset Alzheimer's disease

1994 ◽  
Vol 7 (1) ◽  
pp. 74-78 ◽  
Author(s):  
Cornelia M. van Duijn ◽  
Peter de Knijff ◽  
Marc Cruts ◽  
Anita Wehnert ◽  
Louis M. Havekes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Population Based ◽  
Population Based Study ◽  
Apolipoprotein E4 ◽  
Early Onset Alzheimer’S Disease ◽  
E4 Allele

scholarly journals Cognitive Performance and Cerebrospinal Fluid Markers in Preclinical Alzheimer’s Disease: Results from the Gothenburg H70 Birth Cohort Studies

2021 ◽  
Vol 79 (1) ◽  
pp. 225-235
Author(s):  
Maya Arvidsson Rådestig ◽  
Johan Skoog ◽  
Henrik Zetterberg ◽  
Jürgen Kern ◽  
Anna Zettergren ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cohort Studies ◽  
Cognitive Performance ◽  
Birth Cohort ◽  
Population Based ◽  
Tau Pathology ◽  
Preclinical Alzheimer’S Disease ◽  
Preclinical Ad

Background: We have previously shown that older adults with preclinical Alzheimer’s disease (AD) pathology in cerebrospinal fluid (CSF) had slightly worse performance in Mini-Mental State Examination (MMSE) than participants without preclinical AD pathology. Objective: We therefore aimed to compare performance on neurocognitive tests in a population-based sample of 70-year-olds with and without CSF AD pathology. Methods: The sample was derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden. Participants (n = 316, 70 years old) underwent comprehensive cognitive examinations, and CSF Aβ-42, Aβ-40, T-tau, and P-tau concentrations were measured. Participants were classified according to the ATN system, and according to their Clinical Dementia Rating (CDR) score. Cognitive performance was examined in the CSF amyloid, tau, and neurodegeneration (ATN) categories. Results: Among participants with CDR 0 (n = 259), those with amyloid (A+) and/or tau pathology (T+, N+) showed similar performance on most cognitive tests compared to participants with A-T-N-. Participants with A-T-N+ performed worse in memory (Supra span (p = 0.003), object Delayed (p = 0.042) and Immediate recall (p = 0.033)). Among participants with CDR 0.5 (n = 57), those with amyloid pathology (A+) scored worse in category fluency (p = 0.003). Conclusion: Cognitively normal participants with amyloid and/or tau pathology performed similarly to those without any biomarker evidence of preclinical AD in most cognitive domains, with the exception of slightly poorer memory performance in A-T-N+. Our study suggests that preclinical AD biomarkers are altered before cognitive decline.

Biomarkers and Tools for Predicting Alzheimer’s Disease at the Preclinical Stage

2021 ◽  
Vol 19 ◽  
Author(s):  
Tao-Ran Li ◽  
Qin Yang ◽  
Xiaochen Hu ◽  
Ying Han
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Communication ◽  
High Sensitivity ◽  
Screening Tools ◽  
Therapeutic Window ◽  
Subjective Cognitive Decline ◽  
Preclinical Stage ◽  
Functional Changes ◽  
Preclinical Ad

: Alzheimer’s disease (AD) is the only leading cause of death for which no disease-modifying therapy is currently available. Over the past decade, a string of disappointing clinical trial results has forced us to shift our focus to the preclinical stage of AD, which represents the most promising therapeutic window. However, the accurate diagnosis of preclinical AD requires the presence of brain β-amyloid deposition determined by cerebrospinal fluid or amyloid-positron emission tomography, significantly limiting routine screening and diagnosis in non-tertiary hospital settings. Thus, an easily accessible marker or tool with high sensitivity and specificity is highly needed. Recently, it has been discovered that individuals in the late stage of preclinical AD may not be truly “asymptomatic” in that they may have already developed subtle or subjective cognitive decline. In addition, advances in blood-derived biomarker studies have also allowed detection of pathologic changes in preclinical AD. Exosomes, as cell-to-cell communication messengers, can reflect the functional changes of their source cell. Methodological advances have made it possible to extract brain-derived exosomes from peripheral blood, making exosomes an emerging biomarker carrier and liquid biopsy tool for preclinical AD. The eye and its associated structures have rich sensory-motor innervation. In this regard, studies have indicated that they may also provide reliable markers. Here, our report covers the current state of knowledge of neuropsychological and eye tests as screening tools for preclinical AD and assesses the value of blood and brain-derived exosomes as carriers of biomarkers in conjunction with the current diagnostic paradigm.

scholarly journals Traumatic Brain Injury and Time to Onset of Alzheimer's Disease: A Population-based Study

1999 ◽  
Vol 149 (1) ◽  
pp. 32-40 ◽  
Author(s):  
P. N. Nemetz ◽  
C. Leibson ◽  
J. M. Naessens ◽  
M. Beard ◽  
E. Kokmen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Population Based ◽  
Population Based Study ◽  
Time To Onset
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