Epilepsy and Cognitive Impairments in Alzheimer Disease

By J. Palop, L. Mucke. Archives of Neurology, 2009

678 citations recorded by the source corpus.

Summary Alzheimer disease (AD) is associated with cognitive decline and increased incidence of seizures. Seizure activity in AD has been widely interpreted as a secondary process resulting from advanced stages of neurodegeneration, perhaps in combination with other age-related factors. However, recent findings in animal models of AD have challenged this notion, raising the possibility that aberrant excitatory neuronal activity represents a primary upstream mechanism that may contribute to cognitive deficits in these models. The following observations suggest that such activity may play a similar role in humans with AD: (1) patients with sporadic AD have an increased incidence of seizures that appears to be independent of disease stage and highest in cases with early onset; (2) seizures are part of the natural history of many pedigrees with autosomal dominant early-onset AD, including those with mutations in presenilin-1, presenilin-2, or the amyloid precursor protein, or with duplications of wild-type amyloid precursor protein; (3) inheritance of the major known genetic risk factor for AD, apolipoprotein E4, is associated with subclinical epileptiform activity in carriers without dementia; and (4) some cases of episodic amnestic wandering and disorientation in AD are associated with epileptiform activity and can be prevented with antiepileptic drugs. Here we review recent experimental data demonstrating that high levels of β-amyloid in the brain can cause epileptiform activity and cognitive deficits in transgenic mouse models of AD. We conclude that β-amyloid peptides may contribute to cognitive decline in AD by eliciting similar aberrant neuronal activity in humans and discuss potential clinical and therapeutic implications of this hypothesis.

Subfields: Genetics, Physiology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/aeb49f15ec3ff3a3e625d02db1907380a5aa2520

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Citations in the corpus

Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer’s disease model (2012, background): “AD patients have an increased incidence of epileptic seizures, and the incidence is highest in patients with early-onset AD who overexpress human amyloid precursor protein (hAPP) and Aβ as a result of hAPP gene duplication or trisomy 21 or who carry mutations that alter hAPP processing and Aβ produc”
Seizures and Epileptiform Activity in the Early Stages of Alzheimer Disease (2013, background): “C 10 Atony (1), behavioral arrest (1), epileptic myoclonus (3), generalized tonic-clonic (8), staring spells (1) Language (1), memory (9) Abbreviations: C, convulsive; NC, nonconvulsive.”
Activity Dependent Degeneration Explains Hub Vulnerability in Alzheimer's Disease (2012, background): “Palop & Mucke suggest that amyloid itself causes dysfunction of inhibitory interneurons causing an increase in neuronal activity [46,47], possibly also accounting for the higher prevalence of epileptic activity in AD [48].”
Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. (2010, neutral): “…several APP transgenic strains (Minkevi-ciene et al., 2009; Palop et al., 2007; Palop and Mucke, 2009) and have been associated with AD; the extent of their contribution to pathology, however, remains to be established (Minkeviciene et al., 2009; Palop et al., 2007; Palop and Mucke, 2009).”
Amyloid-β Induced Neuronal Dysfunction in Alzheimer’s Disease: From Synapses toward Neural Networks (2010, background): “, and individuals from many pedigrees with early-onset autosomal dominant Alzheimer's disease have epileptic activit”