Role of Hypertension in Aggravating Aβ Neuropathology of AD Type and Tau-Mediated Motor Impairment

Abstract

Epidemiological evidence suggests that hypertension may accelerate the onset and progression of Alzheimer's disease (AD). In this study, we explored the role of hypertension in the neurodegenerative changes associated with Aβ and tau aggregation. We induced hypertension in APPswe Tg2576 and P301L-tauTg mouse models. In Tg2576 mice, experimental hypertension was associated with a significant increase of the accumulation of Amyloid-β (Aβ) peptides in brain tissue and a significant reduction of Aβ peptides in serum (P < .05). These results indicate that hypertension may promote AD-type Aβ neuropathology in Tg2576. In P301L-tauTg mice we found that the presence of hypertension was significantly associated with aggravated motor function assessed by hindlimb extension test (P = .01). These results suggest that hypertension may play a role in accelerating the progression of motor dysfunction associated with tau-related alterations. Our studies suggest that the management of blood pressure (BP) may alleviate AD-type Aβ neuropathology and neurological disorders associated with abnormal tau metabolism.

Cerebral ischemia aggravates cognitive impairment in a rat model of Alzheimer's disease

“…Neuropathological studies have shown that up to 30% of AD patients exhibit evidence of cerebral infarction, especially striatal lacunar infarction, at autopsy, and that patients with both AD and cerebral infarction show more severe cognitive impairment than those with AD alone (Heyman et al, 1998;Snowdon et al, 1997). It was suggested that hypoxia and vascular risk factors, such as hypertension and diabetes, can accelerate AD development in vivo (Cao et al, 2007;Diaz-Ruiz et al, 2009;Li et al, 2009). Our clinical studies also found that vascular risk factors aggravated the progression of AD (Li et al, 2010(Li et al, , 2011.…”

Review of ‘the Potential Role of Arterial Stiffness in the Pathogenesis of Alzheimer’s Disease’

“…A number of autopsy studies [20,21] have shown that the probability of manifesting clinical dementia for a given level of AD pathology increases with the presence of cerebrovascular pathology, both of which are strongly linked to hypertension [22–30] and arterial stiffness (discussed in detail in the ‘Arterial stiffness & the brain’ section). While there is little mechanistic evidence supporting the observed relationships between blood pressure with the formation of Tau proteins or neurofibrillary tangles in the brain [31,32] , blood pressure may be related to AD pathogenesis or progression through mechanisms involving Aβ synthesis, clearance or its deposition as plaques [33] . Uncontrolled hypertension appears to predict the level of neurofibrillary tangles and neuritic Aβ plaques [34–36] in the brain, which implies hypertension could have direct effects on AD pathology.…”

“…High pulsations in the microvessels of brain and kidneys cause damage to the endothelium with shedding of endothelial cells (the ultimate endothelial dysfunction), causing subsequent thrombosis and microinfarction [47] . High pulsatile pressure stretches and damages all classes of arteries, similar to the effects seen in malignant hypertension and intracerebral hemorrhage [31] resulting in lacunar stroke [24] , microhemorrhage [23] and white matter hyperintensities (WMH) on MRI [22,25] , which are commonly found at autopsy in persons with AD.…”

Stroke risk interacts with Alzheimer's disease biomarkers on brain aging outcomes

“…Similarly, stroke risk factors have shown strong associations with brain volume (Seshadri et al, 2004), neuropsychological impairment (Brady et al, 2001; Jefferson et al, In Press ; Kivipelto et al, 2002), and cerebrovascular pathology (Wang et al, 2009; Wolf et al, 1991). In mouse models, there has been some evidence that certain stroke risk factors, such as smoking (Moreno-Gonzalez et al, 2013) and hypertension (Diaz-Ruiz et al, 2009; Gentile et al, 2009), actually exacerbate AD pathology. Thus, there may be differing effects of stroke risk factors on neurodegeneration depending on the presence or absence of AD biomarkers.…”