Abraham, W. C., Jones, O. D. & Glanzman, D. L. Is plasticity of synapses the mechanism of long-term memory storage? NPJ Sci. Learn. 4, 9 (2019).

Article  PubMed  PubMed Central  Google Scholar 

von Bartheld, C. S. Myths and truths about the cellular composition of the human brain: a review of influential concepts. J. Chem. Neuroanat. 93, 2–15 (2018).

Article  Google Scholar 

Liu, Y. et al. Interactions of glial cells with neuronal synapses, from astrocytes to microglia and oligodendrocyte lineage cells. Glia 71, 1383–1401 (2023).

Article  PubMed  Google Scholar 

Perrone-Capano, C., Volpicelli, F., Penna, E., Chun, J. T. & Crispino, M. Presynaptic protein synthesis and brain plasticity: from physiology to neuropathology. Prog. Neurobiol. 202, 102051 (2021).

Article  CAS  PubMed  Google Scholar 

Chater, T. E., Eggl, M. F., Goda, Y. & Tchumatchenko, T. Competitive processes shape multi-synapse plasticity along dendritic segments. Nat. Commun. 15, 7572 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

De Francesco, S. et al. Differential diagnosis of neurodegenerative dementias with the explainable MRI based machine learning algorithm MUQUBIA. Sci. Rep. 13, 17355 (2023).

Article  PubMed  PubMed Central  Google Scholar 

Henstridge, C. M., Pickett, E. & Spires-Jones, T. L. Synaptic pathology: a shared mechanism in neurological disease. Ageing Res. Rev. 28, 72–84 (2016).

Article  CAS  PubMed  Google Scholar 

DeKosky, S. T. & Scheff, S. W. Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann. Neurol. 27, 457–464 (1990).

Article  CAS  PubMed  Google Scholar 

Terry, R. D. et al. Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann. Neurol. 30, 572–580 (1991).

Article  CAS  PubMed  Google Scholar 

Griffiths, J. & Grant, S. G. N. Synapse pathology in Alzheimer’s disease. Semin. Cell Dev. Biol. 139, 13–23 (2023).

Article  PubMed  Google Scholar 

Frigerio, I. et al. Regional differences in synaptic degeneration are linked to alpha-synuclein burden and axonal damage in Parkinson’s disease and dementia with Lewy bodies. Acta Neuropathol. Commun. 12, 4 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Malpetti, M. et al. Synaptic loss in frontotemporal dementia revealed by [11C]UCB-J positron emission tomography. Ann. Neurol. 93, 142–154 (2023).

Article  PubMed  Google Scholar 

Hermann, P. & Zerr, I. Rapidly progressive dementias — aetiologies, diagnosis and management. Nat. Rev. Neurol. 18, 363–376 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Colom-Cadena, M. et al. Synaptic phosphorylated α-synuclein in dementia with Lewy bodies. Brain 140, 3204–3214 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Clayton, E. L., Huggon, L., Cousin, M. A. & Mizielinska, S. Synaptopathy: presynaptic convergence in frontotemporal dementia and amyotrophic lateral sclerosis. Brain 147, 2289–2307 (2024).

Article  PubMed  PubMed Central  Google Scholar 

Anschuetz, A., Schwab, K., Harrington, C. R., Wischik, C. M. & Riedel, G. A meta-analysis on presynaptic changes in Alzheimer’s disease. J. Alzheimers Dis. 97, 145–162 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Graff-Radford, J. et al. New insights into atypical Alzheimer’s disease in the era of biomarkers. Lancet Neurol. 20, 222–234 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Oh, H. S.-H. et al. A cerebrospinal fluid synaptic protein biomarker for prediction of cognitive resilience versus decline in Alzheimer’s disease. Nat. Med. https://doi.org/10.1038/s41591-025-03565-2 (2025).

Sogorb-Esteve, A. et al. Differential impairment of cerebrospinal fluid synaptic biomarkers in the genetic forms of frontotemporal dementia. Alzheimers Res. Ther. 14, 118 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Borczyk, M., Radwanska, K. & Giese, K. P. The importance of ultrastructural analysis of memory. Brain Res. Bull. 173, 28–36 (2021).

Article  CAS  PubMed  Google Scholar 

Taoufik, E., Kouroupi, G., Zygogianni, O. & Matsas, R. Synaptic dysfunction in neurodegenerative and neurodevelopmental diseases: an overview of induced pluripotent stem-cell-based disease models. Open. Biol. 8, 180138 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Nilsson, J. et al. Cerebrospinal fluid biomarker panel for synaptic dysfunction in a broad spectrum of neurodegenerative diseases. Brain 147, 2414–2427 (2024).

Article  PubMed  PubMed Central  Google Scholar 

Meftah, S. & Gan, J. Alzheimer’s disease as a synaptopathy: evidence for dysfunction of synapses during disease progression. Front. Synaptic Neurosci. 15, 1129036 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Minoshima, S., Cross, D., Thientunyakit, T., Foster, N. L. & Drzezga, A. 18F-FDG PET imaging in neurodegenerative dementing disorders: insights into subtype classification, emerging disease categories, and mixed dementia with copathologies. J. Nucl. Med. 63, 2S–12S (2022).

Article  CAS  PubMed  Google Scholar 

Martínez-Serra, R., Alonso-Nanclares, L., Cho, K. & Giese, K. P. Emerging insights into synapse dysregulation in Alzheimer’s disease. Brain Commun. 4, fcac083 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Goossens, J. et al. Evaluation of cerebrospinal fluid levels of synaptic vesicle protein, VAMP-2, across the sporadic Alzheimer’s disease continuum. Alzheimers Res. Ther. 15, 186 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Martín-de-Saavedra, M. D., Santos, M. D. & Penzes, P. Intercellular signaling by ectodomain shedding at the synapse. Trends Neurosci. 45, 483–498 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Cheng, Q. et al. Biomarkers of synaptic degeneration in Alzheimer’s disease. Ageing Res. Rev. https://doi.org/10.1016/j.arr.2024.102642 (2024).

Iascone, D. M. et al. Whole-neuron synaptic mapping reveals spatially precise excitatory/inhibitory balance limiting dendritic and somatic spiking. Neuron 106, 566–578.e8 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lauterborn, J. C. et al. Increased excitatory to inhibitory synaptic ratio in parietal cortex samples from individuals with Alzheimer’s disease. Nat. Commun. 12, 2603 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tok, S., Ahnaou, A. & Drinkenburg, W. Functional neurophysiological biomarkers of early-stage Alzheimer’s disease: a perspective of network hyperexcitability in disease progression. J. Alzheimers Dis. 88, 809–836 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Targa Dias Anastacio, H., Matosin, N. & Ooi, L. Neuronal hyperexcitability in Alzheimer’s disease: what are the drivers behind this aberrant phenotype? Transl. Psychiatry 12, 257 (2022).

Article  CAS  PubMed