Dementia associated with lacunar infarction.

Loeb, C; Gandolfo, Carlo; Croce, Ronald V.; Conti, Maurizio

doi:10.1161/01.str.23.9.1225

Cited by 158 publications

(127 citation statements)

References 35 publications

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“…The prevalence of dementia in ischemic stroke patients is nine times higher than controls at 3 months (1) and 4 -12 times higher than in controls at 4 years after a lacunar infarct (2). Many of these dementias developed progressively, and cerebral damage is believed to be the direct cause of cognitive decline in only half of these cases (3).…”

Section: From the Departments Of ‡Pharmacology And Neuroscience And §mentioning

confidence: 99%

Transient Cerebral Ischemia Induces Aberrant Neuronal Cell Cycle Re-entry and Alzheimer's Disease-like Tauopathy in Female Rats

Yang

Liu

et al. 2004

Journal of Biological Chemistry

136

134

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Aberrant mitosis occurs in many tauopathy-related neurodegenerative diseases and is believed to precede the formation of neurofibrillary tangles. In this study, we report for the first time that transient cerebral ischemia induces aberrant mitotic proteins and hyperphosphorylation of tau protein with neurofibrillary tanglelike conformational epitopes in adult female rat cortex. Following transient cerebral ischemia in rats, initiation of apoptosis precedes and is potentially integrated with subsequent aberrant mitosis and tau hyperphosphorylation. Furthermore, inhibition of mitosis-related cyclindependent kinases (Cdks) by roscovitine significantly reduced the hyperphosphorylation of tau. Administration of the female sex steroid and potent neuroprotective agent, 17␤-estradiol, reduced ischemia-reperfusioninduced cerebral damage and the subsequent aberrant mitosis and tauopathies. These results provide a neuropathological basis for the higher prevalence of dementia in stroke patients and support the hypothesis that apoptosis and aberrant mitosis are integrated pathological events in neurons that may play a critical role in the development of Alzheimer's disease and other tauopathy-related neuropathology.The prevalence of dementia in ischemic stroke patients is nine times higher than controls at 3 months (1) and 4 -12 times higher than in controls at 4 years after a lacunar infarct (2). Many of these dementias developed progressively, and cerebral damage is believed to be the direct cause of cognitive decline in only half of these cases (3). Alzheimer's disease (AD) 1 is the most prevalent dementia (4) and shares common neuropathology features with stroke. Amyloid angiopathy can lead to cerebral hemorrhage (5), Alz-50-immunoreactive granules are found around cerebral infarction after a stroke (6), amyloid precursor protein accumulates following transient focal ischemia (7), and ApoE4 is a genetic risk factor for both AD and stroke (8).Neurofibrillary tangles (NFTs), whose major component is hyperphosphorylated tau (9), are observed in many neurodegenerative diseases (10, 11). Recent reports indicate that aberrant mitotic activation, as well as DNA replication, in terminally differentiated neurons appears to be involved in the pathogenesis of AD (12, 13). Many cyclin-dependent kinases, including Cdc2 and cyclin B1, as well as many other mitotic markers, are elevated in nearly all tauopathy-related neurodegenerative diseases (14). These protein kinases regulate cell cycle progression into mitosis in developing and proliferating cells. If cell cycle re-entrance is forced by ectopically driving an oncogene with a neuronal-specific promotor, the targeted neurons will die rather than divide (15-18). In AD and other tauopathy diseases, induction of Cdc2 and cyclin B1, as well as aberrant DNA replication, is observed in neurons containing NFTs (13). However, completion of successful nuclear divisions in differentiated neurons has never been reported. These inappropriately induced mitotic protein kinases can phosphorylat...

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Section: From the Departments Of ‡Pharmacology And Neuroscience And §mentioning

confidence: 99%

Transient Cerebral Ischemia Induces Aberrant Neuronal Cell Cycle Re-entry and Alzheimer's Disease-like Tauopathy in Female Rats

Yang

Liu

et al. 2004

Journal of Biological Chemistry

136

134

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“…Moreover, subjects with subcortical vascular disease are at increased risk for developing dementia [6][7][8]11,18,25,28,35,36,39]. Clinicopathological studies have found that, for any level of cognitive deficit, the density of neuritic plaques and neurofibrillary tangles in the neocortex is Du 4 significantly lower in cases of AD mixed with cerebrovascular disease than in cases of AD without cerebrovascular disease [32,35,40], suggesting that cerebrovascular disease has effects in addition to AD pathology on cognition.…”

Section: Introductionmentioning

confidence: 99%

White matter lesions are associated with cortical atrophy more than entorhinal and hippocampal atrophy

Schuff

Chao

et al. 2005

Neurobiology of Aging

108

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“…The proportion of vascular dementia (VaD) attributed to SIVD ranges from 36 to 50%, with higher rates noted among African Americans 1 and Asian Americans 2 than whites. 3,4 A few studies report risk of dementia to be higher among subjects with lacunar infarcts versus other subtypes of stroke, 4 and among patients with AD with concomitant lacunar versus large-artery infarcts. 5 Thus, SIVD is an important subtype of VaD either alone or in combination with AD.…”

mentioning

confidence: 99%

Hippocampal and cortical atrophy predict dementia in subcortical ischemic vascular disease

et al. 2000

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Dementia associated with lacunar infarction.

Cited by 158 publications

References 35 publications

Transient Cerebral Ischemia Induces Aberrant Neuronal Cell Cycle Re-entry and Alzheimer's Disease-like Tauopathy in Female Rats

Transient Cerebral Ischemia Induces Aberrant Neuronal Cell Cycle Re-entry and Alzheimer's Disease-like Tauopathy in Female Rats

White matter lesions are associated with cortical atrophy more than entorhinal and hippocampal atrophy

Hippocampal and cortical atrophy predict dementia in subcortical ischemic vascular disease

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