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Here, we used a novel approach combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to probe cortical excitability in different brain areas known to be directly involved in AD pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed TMS\u2010EEG recordings targeting the left dorsolateral prefrontal cortex (l\u2010DLPFC), the left posterior parietal cortex (l\u2010PPC), and the precuneus (PC) in a large sample of patients with mild\u2010to\u2010moderate AD (n\u00a0=\u00a065) that were compared with a group of age\u2010matched healthy controls (n\u00a0=\u00a021).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that patients with AD are characterized by a regional cortical hyperexcitability in the PC and, to some extent, in the frontal lobe, as measured by TMS\u2010evoked potentials. Notably, cortical excitability assessed over the l\u2010PPC was comparable between the 2 groups. Furthermore, we found that the individual level of PC excitability was associated with the level of cognitive impairment, as measured with Mini\u2010Mental State Examination, and with corticospinal fluid levels of A\u03b2\n                      <jats:sub>42<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Our data provide novel evidence that precuneus cortical hyperexcitability is a key feature of synaptic dysfunction in patients with AD. The current results point to the combined approach of TMS and EEG as a novel promising technique to measure hyperexcitability in patients with AD. This index could represent a useful biomarker to stage disease severity and evaluate response to novel therapies. 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