Cerebral hypoperfusion is not associated with an increase in amyloid β pathology in middle‐aged or elderly people

Abstract

IntroductionIt is hypothesized that cerebral hypoperfusion promotes the development of Alzheimer pathology. We therefore studied whether longstanding cerebral hypoperfusion is associated with Alzheimer pathology in nondemented humans.MethodsCerebral blood flow and amyloid β (18F-Flutemetamol) positron emission tomography retention were assessed in eleven patients with unilateral occlusion of precerebral arteries resulting in chronic and uneven hypoperfusion. A subset of patients underwent tau (18F-AV-1451) positron emission tomography.ResultsThe blood flow was significantly reduced on the affected side of the brain in patients with unilateral occlusion of the internal carotid artery or stenosis of the middle cerebral artery. However, the cortical uptake of 18F-Flutemetamol or 18F-AV-1451 was not altered.DiscussionOur results suggest that longstanding cerebral hypoperfusion in humans does not result in accumulation of amyloid β fibrils or tau aggregates.

Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia

“…In our study, neither IMT nor carotid plaques were significantly associated with AD pathology measured as abnormal CSF Aβ 42 and CSF Aβ 42 /p‐tau ratio in a cognitively unimpaired subcohort (n = 330). This finding is in line with a previous cross‐sectional study on IMT and Aβ PET and a small study of participants with unilaterally occluded carotid arteries, where no association between hypoperfusion and Aβ or tau accumulation was found . Our results may be interpreted as being suggestive of an association between higher IMT and abnormal AD biomarkers (OR = 1.28 and 1.35; see Table ) although encompassing statistical uncertainty because the CIs overlap 1, which may be due to the relatively small sample size yielding large CIs.…”

“…This finding is in line with a previous cross-sectional study on IMT and Aβ PET 15 and a small study of participants with unilaterally occluded carotid arteries, where no association between hypoperfusion and Aβ or tau accumulation was found. 30 Our results may be interpreted as being suggestive of an association between higher IMT and abnormal AD biomarkers (OR = 1.28 and 1.35; see Table 3) although encompassing statistical uncertainty because the CIs overlap 1, which may be due to the relatively small sample size yielding large CIs. Indeed, some neuropathological 31 and experimental 32 studies suggest a link between intracerebral atherosclerosis and Aβ pathology, possibly mediated by hypoxia leading to increased Aβ cleavage and accumulation via enzymatic upregulation as well as by vascular narrowing leading to reduced Aβ clearance.…”

A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer’s Disease Neuropathology

“…CBVD can lead to cerebral hypoperfusion that could result in degradation of the neurovascular unit and subsequent deposition of beta-amyloid and tau, eventually leading to dementia (this vascular pathway has been the focus of several literature reviews [70–72]). The relationship between cerebral blood flow and ADNP remains inconclusive, given a recent study that found no association between cerebral blood flow and cortical uptake of amyloid (flutemetamol) or tau (AV-1451) tracers on PET imaging in 11 middle-aged to elderly patients with unilateral occlusion of precerebral arteries [73]. …”

Association between atherosclerosis and Alzheimer's disease: A systematic review and meta‐analysis

“…A study with 130 samples suggested a negative correlation between CIMT and the MMSE score (Zhou et al, 2016). On the other hand, some researchers found no significant association between the severity of stenosis of carotid and intracranial arteries and cognitive impairment (Lopez‐Oloriz et al, 2013), and decreased brain blood flow caused by atherosclerosis might not lead to increased deposition of Aβ and hyperphosphorylation of tau protein (Hansson et al, 2018).…”