Together, the sex difference in the association between APOE and CSF measures of tau and the lack of a sex difference in the association with neurofibrillary tangles at autopsy suggest that APOE may modulate risk for neurodegeneration in a sex-specific manner, particularly in the presence of amyloidosis.
Our findings suggest that a high ABI, possibly related to arterial stiffness, is associated with elevated brain Aβ burden in cognitively healthy elderly individuals, particularly in APOE ε4 carriers.
Herein, we tested whether anti-human apoE antibodies can decrease Aβ pathology in mice producing both human Aβ and apoE4, and investigated the mechanism underlying these effects.
One model was run for each AD risk factor, including: objectively-defined subtle cognitive decline (Obj-SCD), and genetic susceptibility [apolipoprotein E ε4 (APOE ε4) as well as cerebrospinal fluid β-amyloid (Aβ), total tau (tau), and hyperphosphorylated tau (p-tau).
APOE ε4, the major genetic risk factor for late-onset AD, has been associated with smaller volume in these regions before amyloidosis can be detected by AD biomarkers.
Additionally, apolipoprotein E (APOE), the major genetic risk factor for AD, is predominantly secreted by astrocytes and plays a critical role in amyloid clearance and regulates glucose metabolism in an amyloid-independent manner.
The object of this study was to elucidate the effect of age in the relationship between APOE genotype and CSF biomarkers amyloid-beta1-42 (Abeta42), total tau (tau) and tau phosphorylated at threonine 181 (ptau-181) in AD and controls.
We found that (1) ε4 was associated with decreased CSF beta-amyloid (Aβ1-42) and increased cerebral Aβ deposition across the AD spectrum; (2) increased CSF tau, P-tau and cerebral hypometabolism, hippocampal atrophy, and cognition decline were all associated with APOE ε4 in prodromal AD stage; (3) increased CSF tau, P-tau and cerebral hypometabolism appear to begin earlier than hippocampal atrophy and cognitive decline.
These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer's disease.
We analyzed 28 subjects with apolipoprotein E4 (ApoE4; E4 group) and 89 subjects without ApoE4 (non-E4 group) to determine the association between cortical Aβ accumulation by standard uptake value ratio with [<sup>18</sup>F]florbetapir positron emission tomography and plasma Aβ<sub>1-40</sub> and Aβ<sub>1-42</sub>.
Molecular and genetic findings have provided significant insights into the roles that amyloid, tau, and apolipoprotein E isoforms have in the causation of AD.
In recent research, apolipoprotein-E (apoE) polymorphism has been shown to influence the formation of neurofibrillary changes and the accumulation of beta/A4-amyloid, the histopathological hallmarks of Alzheimer's disease (AD).
The effects of established biomarkers of AD (cerebrospinal fluid tau and amyloid-beta42, positron emission tomography Pittsburgh compound-B, and apolipoprotein E [APOE] genotype) on concurrent cognitive performance in cognitively normal individuals have been mixed.
As apolipoprotein E (ApoE), a lipid-transporting protein with three human isoforms (E2, E3, and E4), also binds to Aβ, we hypothesized that ApoE and fibrin(ogen) may have a combined effect on the vascular pathophysiology in AD.
Rapidly progressive Alzheimer's disease that is associated with a low frequency of APOE e4 allele demonstrates considerably expanded conformational heterogeneity of amyloid-β42, with higher levels of distinctly structured amyloid-β42 particles composed of 30-100 monomers, and fewer particles composed of < 30 monomers.
beta-Amyloid (Abeta) deposits are found in the brains of approximately one-third of patients who die within days after a severe head injury; their presence correlating strongly with possession of an apolipoprotein E (apoE)-epsilon4 allele.
The examined predictors of Aβ status were demographics; cognitive tests; white matter lesions; apolipoprotein E (APOE); and plasma Aβ<sub>42</sub>/Aβ<sub>40</sub>, tau, and neurofilament light.
We have previously shown that the presence of ApoE4 renders neurons unresponsive to Reelin by impairing the recycling of the receptors, thereby decreasing its protective effects against amyloid β (Aβ) oligomer-induced synaptic toxicity in vitro.
To determine whether serum Apolipoprotein E (Apo E) type 4 isoprotein is a risk factor for the development of amyloidosis in patients with rheumatoid arthritis (RA).