Jack CR, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535–562.
Braak H, Tredici K Del. Neuroanatomy and Pathology of Sporadic Parkinson’s Disease. Springer Berlin Heidelberg; 2015.
Braak H, et al. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol. 2011;70(11):960–969.
Braak H, Del Tredici K. The pathological process underlying Alzheimer’s disease in individuals under thirty. Acta Neuropathol. 2011;121(2):171–181.
Ehrenberg AJ, et al. Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer’s disease. Neuropathol Appl Neurobiol. 2017;43(5):393–408.
Braak H, Del Tredici K. The preclinical phase of the pathological process underlying sporadic Alzheimer’s disease. Brain. 2015;138(10):2814–2833.
Grothe MJ, et al. In vivo staging of regional amyloid deposition. Neurology. 2017;89(20):2031–2038.
Tracy TE, Gan L. Tau-mediated synaptic and neuronal dysfunction in neurodegenerative disease. Curr Opin Neurobiol. 2018;51:134–138.
D’Amelio M, Rossini PM. Brain excitability and connectivity of neuronal assemblies in Alzheimer’s disease: from animal models to human findings. Prog. Neurobiol. 2012;99(1):42–60.
Olazarán J, et al. Cortical excitability in very mild Alzheimer’s disease: a long-term follow-up study. J Neurol. 2010;257(12):2078–2085.
Ferreri F, et al. Motor cortex excitability in Alzheimer’s disease: a transcranial magnetic stimulation follow-up study. Neurosci. Lett. 2011;492(2):94–98.
Casarotto S, et al. Transcranial magnetic stimulation-evoked EEG/cortical potentials in physiological and pathological aging. Neuroreport. 2011;22(12):592–597.
Trebbastoni A, et al. Altered cortical synaptic plasticity in response to 5-Hz repetitive transcranial magnetic stimulation as a new electrophysiological finding in amnestic mild cognitive impairment converting to Alzheimer’s disease: results from a 4-year prospective cohort s. Front Aging Neurosci. 2016;7:253.
Yamada K, et al. Neuronal activity regulates extracellular tau in vivo. J Exp Med. 2014;211(3):387–393.
Bero AW, et al. Neuronal activity regulates the regional vulnerability to amyloid-ß deposition. Nat Neurosci. 2011;14(6):750–756.
Holth JK,et al. The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans. Science. 2019;363(6429):880–884.
Ooms SJ, et al. Effect of 1 night of total sleep deprivation on cerebrospinal fluid ß-amyloid 42 in healthy middle-aged men: a randomized clinical trial. JAMA Neurol. 2014;71(8):971–977.
Herring A, et al. Amyloid-β dimers in the absence of plaque pathology impair learning and synaptic plasticity. Brain. 2015;139(2015):1–525.
Bellucci A, et al. Induction of inflammatory mediators and microglial activation in mice transgenic for mutant human P301S tau protein. Am J Pathol. 2004;165(5):1643–1652.
Laurent C, et al. Tau and neuroinflammation: what impact for Alzheimer’s disease and tauopathies?. Biomed J. 2018;41(1):21–33.
De Calignon A, et al. Propagation of tau pathology in a model of early Alzheimer’s disease. Neuron. 2012;73(4):685–697.
Asai H, et al. Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat Neurosci. 2015;18(11):1584–1593.
Maphis N, et al. Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain. Brain. 2015;138(6):1738–1755.
Holth JK, et al. Tau loss attenuates neuronal network hyperexcitability in mouse and drosophila genetic models of epilepsy. J Neurosci. 2013;33(4):1651–1659.
Hall AM, et al. Tau-dependent Kv4.2 depletion and dendritic hyperexcitability in a mouse model of Alzheimer’s disease. J Neurosci. 2015;35(15):6221–6230.
Schultz MK, et al. Pharmacogenetic neuronal stimulation increases human tau pathology and trans-synaptic spread of tau to distal brain regions in mice. Neurobiol Dis. 2018;118:161–176.
Pasquini L, et al. Medial temporal lobe disconnection and hyperexcitability across Alzheimer’s disease stages. J Alzheimers Dis Rep. 2019;3(1):103–112.
Jagust W. Imaging the evolution and pathophysiology of Alzheimer disease. Nat Rev Neurosci. 2018;19(11):687–700.
Harada R, et al. Correlations of 18 F-THK5351 PET with post-mortem burden of tau and astrogliosis in Alzheimer’s disease. J Nucl Med. 2018;59(4):671–674.
Murugan NA, et al. Cross-interaction of tau PET tracers with monoamine oxidase B: evidence from in silico modelling and in vivo imaging. Eur J Nucl Med Mol Imaging. 2019;46(6):1369–1382.
Lemoine L, et al. Comparative binding properties of the tau PET tracers THK5117, THK5351, PBB3, and T807 in postmortem Alzheimer brains. Alzheimers Res Ther. 2017;9(1):96.
Ishiki A, et al. Neuroimaging-pathological correlations of [18F]THK5351 PET in progressive supranuclear palsy. Acta Neuropathol Commun. 2018;6(1):53.
Heneka MT, et al. Locus ceruleus controls Alzheimer’s disease pathology by modulating microglial functions through norepinephrine. Proc Natl Acad Sci U S A. 2010;107(13):6058–6063.
Satoh A, Iijima KM. Roles of tau pathology in the locus coeruleus (LC) in age-associated pathophysiology and Alzheimer’s disease pathogenesis: potential strategies to protect the LC against aging. Brain Res. 2019;1702:17–28.
Mueller A, et al. Tau PET imaging with 18F-PI-2620 in patients with Alzheimer disease and healthy controls: a first-in-humans study. J Nucl Med. 2020;61(6):911–919.
Leuzy A, et al. Diagnostic performance of RO948 F 18 Tau positron emission tomography in the differentiation of Alzheimer disease from other neurodegenerative disorders. JAMA Neurol. 2020;77(8):955–965.
Schöll M, et al. Biomarkers for tau pathology. Mol Cell Neurosci. 2019;97:18–33.
de Haan W, et al. Altering neuronal excitability to preserve network connectivity in a computational model of Alzheimer’s disease. PLoS Comput Biol. 2017;13(9):e1005707.
Palop JJ, Mucke L. Amyloid-β–induced neuronal dysfunction in Alzheimer’s disease: from synapses toward neural networks. Nat Neurosci. 2010;13(7):812–818.
Kellner V, et al. Amyloid-β alters ongoing neuronal activity and excitability in the frontal cortex. Neurobiol Aging. 2014;35(9):1982–1991.
Clewett DV, et al. Neuromelanin marks the spot: identifying a locus coeruleus biomarker of cognitive reserve in healthy aging. Neurobiol Aging. 2016;37:117–126.
Roberson ED, et al. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer’s disease mouse model. Science. 2007;316(5825):750–754.
DeVos SL, et al. Antisense reduction of tau in adult mice protects against seizures. J Neurosci. 2013;33(31):12887–12897.
Busche MA, et al. Decreased amyloid-β and increased neuronal hyperactivity by immunotherapy in Alzheimer’s models. Nat Neurosci. 2015;18(12):1725–1727.
Mucke L, Selkoe DJ. Neurotoxicity of amyloid β-protein: synaptic and network dysfunction. Cold Spring Harb Perspect Med. 2012;2(7):a006338.
Crimins JL, et al. Electrophysiological changes precede morphological changes to frontal cortical pyramidal neurons in the rTg4510 mouse model of progressive tauopathy. Acta Neuropathol. 2012;124(6):777–795.
Andrews-Zwilling Y, et al. Apolipoprotein E4 causes age- and tau-dependent impairment of GABAergic interneurons, leading to learning and memory deficits in mice. J Neurosci. 2010;30(41):13707–13717.
Huber R, et al. Human cortical excitability increases with time awake. Cereb Cortex. 2013;23(2):332–338.
Ly JQM, et al. Circadian regulation of human cortical excitability. Nat Commun. 2016;7:11828.
Van Egroo M, et al. Preserved wake-dependent cortical excitability dynamics predict cognitive fitness beyond age-related brain alterations. Commun Biol. 2019;2:449.
Gaggioni G, et al. Age-related decrease in cortical excitability circadian variations during sleep loss and its links with cognition. Neurobiol Aging. 2019;78:52–63.
Mattis S. Mental status examination for organic mental syndrome in the elderly patients. In: Bellak L, Karasu TB, eds. Geriatric Psychiatry. Grune & Stratton: 1976:77–121.
Beck AT, et al. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol. 1988;56(6):893–897.
Beck AT, et al. Psychometric properties of the beck depression inventory: twenty-five years of evaluation. Clin Psychol Rev. 1988;8(1):77–100.
Virtanen J, et al. Instrumentation for the measurement of electric brain responses to transcranial magnetic stimulation. Med Biol Eng Comput. 1999;37(3):322–326.
Weiskopf N, Helms G. Multi-parameter mapping of the human brain at 1mm resolution in less than 20 minutes. Proc Intl Soc Mag Reson Med. 2008;16:2241.
Tabelow K, et al. hMRI — a toolbox for quantitative MRI in neuroscience and clinical research. Neuroimage. 2019;194:191–210.
Ashburner J, Friston KJ. Diffeomorphic registration using geodesic shooting and Gauss-Newton optimisation. Neuroimage. 2011;55(3):954–967.
Lambert C, et al. Multiparametric brainstem segmentation using a modified multivariate mixture of Gaussians. Neuroimage Clin. 2013;2(1):684–694.
Lockhart SN, et al. Dynamic PET measures of tau accumulation in cognitively normal older adults and Alzheimer’s disease patients measured using [18F] THK-5351. PLoS One. 2016;11(6):e0158460.
Klunk WE, et al. The Centiloid Project: standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement. 2015;11(1):1–15.e1–4.
Battle MR, et al. Centiloid scaling for quantification of brain amyloid with [18F]flutemetamol using multiple processing methods. EJNMMI Res. 2018;8(1):107.
Navitsky M, et al. Standardization of amyloid quantitation with florbetapir standardized uptake value ratios to the Centiloid scale. Alzheimers Dement. 2018;14(12):1565–1571.
Tzourio-Mazoyer N, et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage. 2002;15(1):273–289.
Chiotis K, et al. Dual tracer tau PET imaging reveals different molecular targets for 11C-THK5351 and 11C-PBB3 in the Alzheimer brain. Eur J Nucl Med Mol Imaging. 2018;45(9):1605–1617.
Jaeger BC, et al. An R2 statistic for fixed effects in the generalized linear mixed model. J Appl Stat. 2017;44(6):1086–1105.
