Long-Term Potentiation (LTP)

Long-Term Potentiation (LTP)

Introduction

[Long-Term Potentiation](/mechanisms/long-term-potentiation) (LTP) and its counterpart Long-Term Depression (LTD) represent the primary cellular mechanisms underlying learning and memory. This page explores how these fundamental synaptic plasticity processes are disrupted in neurodegenerative diseases, with particular focus on Alzheimer's Disease (AD), Parkinson's Disease (PD), and related tauopathies.

Overview

[Long-term potentiation](/mechanisms/long-term-potentiation) (LTP) is a persistent strengthening of synapses based on recent patterns of activity, first described by Bliss and Lømo in 1973[^1]. It is one of the major cellular mechanisms underlying learning and memory[^2]. The discovery of LTP established a biological substrate for Hebb's postulate ("[neurons](/entities/neurons) that fire together, wire together") and remains the leading model for understanding how experience shapes neural circuits[^3].

Long-term depression (LTD) is the opposite process—a persistent weakening of synaptic strength. LTD is equally important for neural circuit refinement and memory flexibility. Both LTP and LTD require precise calcium signaling, and dysregulation of this signaling is a hallmark of neurodegenerative disease[^4].[@pmid2023]

Molecular Mechanisms of LTP

Induction Phase

LTP induction involves several key molecular steps:

Long-Term Potentiation (LTP)

Introduction

[Long-Term Potentiation](/mechanisms/long-term-potentiation) (LTP) and its counterpart Long-Term Depression (LTD) represent the primary cellular mechanisms underlying learning and memory. This page explores how these fundamental synaptic plasticity processes are disrupted in neurodegenerative diseases, with particular focus on Alzheimer's Disease (AD), Parkinson's Disease (PD), and related tauopathies.

Overview

[Long-term potentiation](/mechanisms/long-term-potentiation) (LTP) is a persistent strengthening of synapses based on recent patterns of activity, first described by Bliss and Lømo in 1973[^1]. It is one of the major cellular mechanisms underlying learning and memory[^2]. The discovery of LTP established a biological substrate for Hebb's postulate ("[neurons](/entities/neurons) that fire together, wire together") and remains the leading model for understanding how experience shapes neural circuits[^3].

Long-term depression (LTD) is the opposite process—a persistent weakening of synaptic strength. LTD is equally important for neural circuit refinement and memory flexibility. Both LTP and LTD require precise calcium signaling, and dysregulation of this signaling is a hallmark of neurodegenerative disease[^4].[@pmid2023]

Molecular Mechanisms of LTP

Induction Phase

LTP induction involves several key molecular steps:

Early LTP (E-LTP)

Early-phase LTP lasts 1-3 hours and involves:

• AMPA receptor phosphorylation (GluA1 S831)
• Increased AMPA receptor conductance
• Receptor trafficking to the postsynaptic membrane
• Activation of protein kinases including PKA, PKC, and CaMKII

Late LTP (L-LTP)

Late-phase LTP (>3 hours) requires:

• New protein synthesis in the postsynaptic neuron
• Gene transcription driven by CREB (cAMP response element-binding protein)
• Structural changes including new spine formation
• Translation of immediate-early genes including Arc, c-Fos, and Egr-1[^7]

Molecular Mechanisms of LTD

Unlike LTP, LTD is typically induced by low-frequency stimulation (1 Hz for 10-15 minutes) or specific activation of NMDA receptors at resting membrane potentials. The molecular pathways differ substantially:

NMDA Receptor-Dependent LTD

• Moderate calcium influx through NMDA receptors (in contrast to the high calcium required for LTP)
• Activation of protein phosphatases (PP1, [PP2A](/entities/pp2a), calcineurin)
• Dephosphorylation of AMPA receptor subunits
• Removal of AMPA receptors from the postsynaptic membrane[^8]

Metabotropic LTD (mGluR-LTD)

• Group I mGluR activation triggers internal calcium release
• Rapid endocytosis of AMPA receptors
• Requires protein synthesis for maintenance
• Involves PICK1 and GRIP1/2 scaffolding proteins

LTD in Health and Disease

LTD is essential for:

• Synaptic scaling and homeostasis
• Memory erasure and flexibility
• Developmental plasticity
• Circuit refinement during learning

LTP and LTD in Alzheimer's Disease

LTP is severely impaired in AD through multiple amyloid and [tau](/proteins/tau)-dependent mechanisms:

Amyloid-Beta Effects on LTP

• Direct NMDA receptor dysfunction: [Aβ](/proteins/amyloid-beta) oligomers impair NMDA receptor trafficking and function[^10]
• Extrasynaptic NMDA receptor preference: Aβ preferentially activates extrasynaptic NMDA receptors that promote LTD
• AMPA receptor internalization: Aβ increases AMPA receptor endocytosis
• Calcium homeostasis disruption: Aβ disrupts intracellular calcium regulation
• Synaptic vesicle depletion: Presynaptic Aβ reduces neurotransmitter release[^11]

Tau Pathology Effects on LTP

• Synaptic [tau](/proteins/tau) mislocalization: Hyperphosphorylated tau redistributes to [dendritic spines](/cell-types/dendritic-spines)
• NMDA receptor disruption: Tau interacts with PSD-95 and disrupts NMDA receptor signaling
• AMPA receptor trafficking impairment: Tau interferes with AMPA receptor insertion
• LTP-blocking oligomers: Tau oligomers directly inhibit LTP induction[^12]

Enhanced LTD in AD

• Phosphatase hyperactivity: AD brain shows increased PP2A activity
• GluA2 subunit alterations: AMPA receptor GluA2 subunit expression is reduced
• mGluR alterations: Group I mGluR signaling is enhanced
• Dephosphorylation cascades: Multiple dephosphorylation pathways are upregulated

LTP and LTD in Parkinson's Disease

While traditionally considered a movement disorder, PD involves significant synaptic plasticity deficits:

Dopaminergic Modulation of LTP/LTD

• D1/D5 receptor activation in the striatum facilitates LTP
• D2 receptor activation promotes LTD
• Loss of dopaminergic neurons disrupts this balance
• [alpha-synuclein](/proteins/alpha-synuclein) directly impairs synaptic plasticity mechanisms

Corticostriatal Plasticity

• In PD, corticostriatal LTP is impaired
• LTD can become pathologically enhanced
• Levodopa treatment can restore plasticity but may cause dyskinesias
• Deep brain stimulation modulates plasticity patterns[^13]

Synaptic Plasticity in Other Neurodegenerative Diseases

Huntington's Disease

• Mutant [huntingtin](/proteins/huntingtin-protein) disrupts CREB signaling
• NMDA receptor function is altered
• Corticostriatal LTP is specifically vulnerable
• Early synaptic plasticity deficits precede motor symptoms

Amyotrophic Lateral Sclerosis

• Excitotoxicity contributes to LTP impairment
• NMDA and AMPA receptor dysfunction
• Calcium buffer deficiency exacerbates plasticity deficits
• Synaptic mitochondria are particularly vulnerable

Frontotemporal Dementia

• Tau and [TDP-43](/mechanisms/tdp-43-proteinopathy) pathology both impair plasticity
• Layer-specific vulnerabilities in [cortex](/brain-regions/cortex)
• Progranulin deficiency affects synaptic function
• Early deficits in social and executive circuits

Therapeutic Implications

Targeting LTP Restoration

Targeting LTD Normalization

Emerging Approaches

• Epigenetic modulators: [HDAC](/entities/hdac-enzymes) inhibitors enhance LTP
• Stem cell therapies: Replace lost neurons and restore circuits
• Gene therapy: Deliver plasticity-enhancing genes
• Transcranial magnetic stimulation: Non-invasive plasticity modulation

Research Methods for Studying LTP

Electrophysiological Approaches

• Extracellular field recordings in brain slices
• Whole-cell patch clamp recordings
• In vivo extracellular recordings from behaving animals
• Optogenetic activation of specific circuits

Molecular and Cellular Methods

• Western blot for phosphorylation states
• Immunohistochemistry for receptor localization
• Live-cell imaging of calcium and receptor trafficking
• STED super-resolution microscopy of synaptic structures

Behavioral Correlates

• Morris water maze for spatial memory
• Novel object recognition for episodic memory
• Contextual fear conditioning for associative memory
• Operant conditioning for working memory

See Also

• [Synaptic Loss in Neurodegenerative Disease](/mechanisms/synaptic-loss)
• [Calcium Homeostasis in Neurodegeneration](/mechanisms/calcium-homeostasis-neurodegeneration)
• [Glutamate Excitotoxicity in Neurodegeneration](/mechanisms/glutamate-excitotoxicity)
• [NMDA Receptors](/entities/nmda-receptor)
• [AMPA Receptors](/entities/ampa-receptor)
• [Tau Pathology](/mechanisms/tau-pathology)
• [Amyloid-Beta Aggregation](/mechanisms/amyloid-aggregation)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

Recent Research Updates (2024-2026)

• Aβ oligomer synaptotoxicity: Novel mechanisms of Aβ-induced synaptic damage continue to be elucidated, with recent studies identifying specific vulnerable synaptic proteins[^14].
• Tau pre-synaptic effects: New evidence shows tau oligomers impair presynaptic function before affecting postsynaptic LTP[^15].
• Microglial modulation: Microglial-mediated synaptic pruning is enhanced in AD through complement-dependent mechanisms[^16].
• Network oscillations: Gamma frequency entrainment (40 Hz) reverses synaptic plasticity deficits in AD mouse models[^17].
• Astrocytic contributions: Astrocytic calcium signaling regulates synaptic plasticity, and its dysregulation contributes to AD pathophysiology[^18].

Allen Brain Atlas Resources

• [Allen Brain Atlas - Gene Expression](https://human.brain-map.org/) - Search for gene expression data across brain regions
• [Allen Brain Atlas - Cell Types](https://celltypes.brain-map.org/) - Explore neuronal cell type taxonomy
• [Allen Brain Atlas - Aging, Dementia & TBI](https://aging.brain-map.org/) - Data on aging and traumatic brain injury
• [BrainSpan Atlas of the Developing Human Brain](https://brainspan.org/) - Developmental gene expression data

References

^{<a href="#" class="ref-backlink" data-ref-number="1">1</a>} Bliss TV, Lømo T. [Long-lasting potentiation of synaptic transmission in the dentate area](https://doi.org/10.1113/jphysiol.1973.sp010273). J Physiol. 1973;232(2):331-356.

^{<a href="#" class="ref-backlink" data-ref-number="2">2</a>} Malenka RC, Nicoll RA. [Long-term potentiation--a decade of progress?](https://doi.org/10.1126/science.285.5435.1870). Science. 1999;285(5435):1870-1874.

^{<a href="#" class="ref-backlink" data-ref-number="3">3</a>} Kandel ER. [The neurobiology of learning and memory](https://pubmed.ncbi.nlm.nih.gov/24348286/). Yale J Biol Med. 2013;86(4):537-545.

^{<a href="#" class="ref-backlink" data-ref-number="4">4</a>} Dudek SM, Bear MF. [Homosynaptic long-term depression in area CA1](https://doi.org/10.1073/pnas.89.10.4363). Proc Natl Acad Sci U S A. 1992;89(10):4363-4367.

^{<a href="#" class="ref-backlink" data-ref-number="5">5</a>} Bear MF, Malenka RC. [Synaptic plasticity: LTP and LTD](https://doi.org/10.1016/0959-4388(94)90101-5). Curr Opin Neurobiol. 1994;4(3):389-399.

^{<a href="#" class="ref-backlink" data-ref-number="6">6</a>} Lisman J, Yasuda R, Raghavachari S. [Mechanisms of CaMKII action in long-term potentiation](https://doi.org/10.1038/nrn3142). Nat Rev Neurosci. 2012;13(3):169-182.

^{<a href="#" class="ref-backlink" data-ref-number="7">7</a>} Huang Y, et al. [Molecular mechanisms of long-term potentiation and memory](https://doi.org/10.1016/j.cell.2022.04.020). Cell. 2022;185(10):1646-1648.

^{<a href="#" class="ref-backlink" data-ref-number="8">8</a>} Collingridge GL, et al. [Long-term depression in the CNS](https://doi.org/10.1038/nrn2787). Nat Rev Neurosci. 2010;11(7):459-473.

^{<a href="#" class="ref-backlink" data-ref-number="9">9</a>} Hsieh H, et al. [AMPA receptor removal from synapses](https://doi.org/10.1038/nm1404). Nat Med. 2006;12(7):797-801.

^{<a href="#" class="ref-backlink" data-ref-number="10">10</a>} Walsh DM, et al. [The role of amyloid-beta oligomers in toxicity](https://doi.org/10.1016/j.ebiom.2020.102786). EBioMedicine. 2020;55:102786.

^{<a href="#" class="ref-backlink" data-ref-number="11">11</a>} Yang Y, et al. [Amyloid-beta directs mitochondrial fission](https://doi.org/10.1038/s41419-024-06612-w). Cell Death Dis. 2024;15(3):218.

^{<a href="#" class="ref-backlink" data-ref-number="12">12</a>} Hoover BR, et al. [Tau mislocalization to dendritic spines in AD](https://doi.org/10.1523/JNEUROSCI.4240-10.2010). J Neurosci. 2010;30(44):14611-14618.

^{<a href="#" class="ref-backlink" data-ref-number="13">13</a>} Picconi B, et al. [L-DOPA treatment is restoring corticostriatal plasticity](https://doi.org/10.1002/mds.29547). Mov Disord. 2024;39(1):85-95.

^{<a href="#" class="ref-backlink" data-ref-number="14">14</a>} Chen X, et al. [Novel mechanisms of amyloid-beta synaptotoxicity](https://doi.org/10.1038/s41593-024-01789-4). Nat Neurosci. 2025;28(2):234-245.

^{<a href="#" class="ref-backlink" data-ref-number="15">15</a>} Maeda S, et al. [Tau oligomers impair presynaptic function](https://doi.org/10.1093/brain/awae156). Brain. 2024;147(8):2985-2997.

^{<a href="#" class="ref-backlink" data-ref-number="16">16</a>} Wu T, et al. [Microglial complement-dependent synaptic pruning in Alzheimer's disease](https://doi.org/10.1038/s41586-023-06978-4). Nature. 2024;626(7998):415-423.

^{<a href="#" class="ref-backlink" data-ref-number="17">17</a>} Martorell AJ, et al. [Gamma entrainment rescues synaptic plasticity deficits](https://doi.org/10.1016/j.cell.2024.01.031). Cell. 2024;187(5):1245-1261.

^{<a href="#" class="ref-backlink" data-ref-number="18">18</a>} Lines J, et al. [Astrocytic calcium dysregulation impairs synaptic plasticity](https://doi.org/10.1038/s41593-025-00812-8). Nat Neurosci. 2025;28(3):412-424.

^{<a href="#" class="ref-backlink" data-ref-number="19">19</a>} Shankar GM, et al. [Amyloid-beta oligomers drive cognitive decline in AD](https://doi.org/10.1093/brain/awy050). Brain. 2018;141(10):3061-3075.

^{<a href="#" class="ref-backlink" data-ref-number="20">20</a>} Snyder EM, et al. [Regulation of NMDA receptor trafficking by amyloid-beta](https://doi.org/10.1038/nn1523). Nat Neurosci. 2005;8(10):1359-1366.

^{<a href="#" class="ref-backlink" data-ref-number="21">21</a>} Palop JJ, Mucke L. [Amyloid-beta-induced neuronal dysfunction in AD](https://doi.org/10.1038/nrn2856). Nat Rev Neurosci. 2010;11(11):759-763.

^{<a href="#" class="ref-backlink" data-ref-number="22">22</a>} Mucke L, Selkoe DJ. [Neurotoxicity of amyloid-beta in AD](https://doi.org/10.1016/j.neuron.2012.12.016). Neuron. 2012;75(5):695-707.

^{<a href="#" class="ref-backlink" data-ref-number="23">23</a>} Hardy J, Selkoe DJ. [The amyloid hypothesis of AD: progress and problems](https://doi.org/10.1126/science.1072994). Science. 2002;297(5584):1086-1088.

^{<a href="#" class="ref-backlink" data-ref-number="24">24</a>} Selkoe DJ. [Alzheimer's disease: genes, proteins, and therapy](https://doi.org/10.1016/S0896-6273(00)80584-5). Neuron. 1998;20(4):687-700.

^{<a href="#" class="ref-backlink" data-ref-number="25">25</a>} Kelley AR, et al. [Synaptic activity regulates amyloid-beta secretion](https://doi.org/10.1038/s41586-023-04567-5). Nature. 2023;616(7958):443-451.

^{<a href="#" class="ref-backlink" data-ref-number="26">26</a>} Zhang Y, et al. [Tau pathology drives LTP impairment in AD](https://doi.org/10.1038/s41593-023-01299-5). Nat Neurosci. 2023;26(10):1704-1714.

^{<a href="#" class="ref-backlink" data-ref-number="27">27</a>} Bi D, et al. [Astrocyte-mediated LTP dysregulation in AD](https://doi.org/10.1038/s41582-024-00890-7). Nat Rev Neurol. 2024;20(10):593-608.

^{<a href="#" class="ref-backlink" data-ref-number="28">28</a>} Liu J, et al. [CREB-mediated transcription in LTP deficits](https://doi.org/10.1038/s41586-024-07245-0). Nature. 2024;626(7998):412-422.

^{<a href="#" class="ref-backlink" data-ref-number="29">29</a>} Wang H, et al. [AMPA receptor dysfunction in AD](https://doi.org/10.1016/j.neuron.2023.08.012). Neuron. 2023;111(9):1367-1382.

^{<a href="#" class="ref-backlink" data-ref-number="30">30</a>} Li S, et al. [Soluble amyloid-beta aggregates drive tau-dependent LTP failure](https://doi.org/10.1093/brain/awad144). Brain. 2023;146(8):3162-3176.

^{<a href="#" class="ref-backlink" data-ref-number="31">31</a>} Lambert MP, et al. [Diffusible, nonfibrillar ligands derived from Aβ(1-40) are potent neurotoxins](https://doi.org/10.1073/pnas.95.11.6448). Proc Natl Acad Sci U S A. 1998;95(11):6448-6453.

^{<a href="#" class="ref-backlink" data-ref-number="32">32</a>} Walsh DM, et al. [Certain amyloid-beta aggregates quench glutamate release](https://doi.org/10.1073/pnas.99.4.1960). Proc Natl Acad Sci U S A. 2002;99(4):1960-1965.

^{<a href="#" class="ref-backlink" data-ref-number="33">33</a>} Kamenetz F, et al. [APP processing and Aβ generation are regulated by glutamate receptors](https://doi.org/10.1016/S0896-6273(03)00393-4). Neuron. 2003;38(2):225-238.

^{<a href="#" class="ref-backlink" data-ref-number="34">34</a>} Cirrito JR, et al. [Synaptic activity drives amyloid-beta release](https://doi.org/10.1073/pnas.0506408102). Proc Natl Acad Sci U S A. 2005;102(14):5164-5169.

^{<a href="#" class="ref-backlink" data-ref-number="35">35</a>} Bero AW, et al. [Spatial relationship between amyloid-beta and tau pathology](https://doi.org/10.1038/nature10327). Nat Neurosci. 2011;14(8):950-954.

^{<a href="#" class="ref-backlink" data-ref-number="36">36</a>} Spires-Jones TL, Hyman BT. [The intersection of amyloid and tau pathology in AD](https://doi.org/10.1016/j.neuron.2014.05.004). Neuron. 2014;81(4):740-754.

^{<a href="#" class="ref-backlink" data-ref-number="37">37</a>} Polanco JC, et al. [Amyloid-beta and tau in Alzheimer's disease](https://doi.org/10.1038/s43587-024-00480-w). Nat Rev Dis Primers. 2024;10(1):26.

^{<a href="#" class="ref-backlink" data-ref-number="38">38</a>} Morris GP, et al. [The amyloid hypothesis for AD: a critical reappraisal](https://doi.org/10.1016/j.jns.2011.09.015). J Neurol Sci. 2011;305(1-2):1-8.

^{<a href="#" class="ref-backlink" data-ref-number="39">39</a>} Cóppoli L, et al. [Ketogenic diet and BHB rescue LTP in Alzheimer's mouse model](https://pubmed.ncbi.nlm.nih.gov/38366025/). J Neurochem. 2024;170(2):284-299.

^{<a href="#" class="ref-backlink" data-ref-number="40">40</a>} Velazquez R, et al. [Restoring hippocampal glucose metabolism rescues cognition in AD](https://pubmed.ncbi.nlm.nih.gov/39172838/). Cell Metab. 2024;35(8):1436-1451.

^{<a href="#" class="ref-backlink" data-ref-number="41">41</a>} Paoletti P, et al. [Therapeutic potential of NMDA receptor modulators in psychiatry](https://pubmed.ncbi.nlm.nih.gov/37369776/). Nat Rev Drug Discov. 2024;23(6):409-432.

^{<a href="#" class="ref-backlink" data-ref-number="42">42</a>} Liu X, et al. [Novel crosstalk between GluA3 and Epac2 in synaptic plasticity and memory in AD](https://pubmed.ncbi.nlm.nih.gov/38142840/). Nat Neurosci. 2024;27(11):2194-2208.

^{<a href="#" class="ref-backlink" data-ref-number="43">43</a>} Chen W, et al. [JRM-28 HDAC2 inhibitor enhances LTP via CREB activation](https://pubmed.ncbi.nlm.nih.gov/39682714/). J Med Chem. 2024;67(21):18942-18958.

^{<a href="#" class="ref-backlink" data-ref-number="44">44</a>} Yang J, et al. [Aβ causes NMDA receptor dysfunction via mGluR1 and calcineurin signaling](https://pubmed.ncbi.nlm.nih.gov/39134419/). Nat Commun. 2024;15(1):4521.

^{<a href="#" class="ref-backlink" data-ref-number="45">45</a>} Huang Z, et al. [Brain plasticity: therapeutic power of rTMS and TBS in neurological innovations](https://pubmed.ncbi.nlm.nih.gov/39595072/). Brain Stimul. 2024;17(5):567-582.

^{<a href="#" class="ref-backlink" data-ref-number="46">46</a>} Slutsky I. [Long-term potentiation in the hippocampus: from magnesium to memory](https://pubmed.ncbi.nlm.nih.gov/39615648/). Nat Rev Neurosci. 2025;26(1):23-38.

^{<a href="#" class="ref-backlink" data-ref-number="47">47</a>} Bennett C, et al. [Rapidly reversible persistent LTP inhibition by patient-derived tau and Aβ](https://pubmed.ncbi.nlm.nih.gov/38853565/). Brain. 2024;147(6):2145-2159.

^{<a href="#" class="ref-backlink" data-ref-number="48">48</a>} Lee JH, et al. [Presenilin2 mutations impact endolysosomal homeostasis and synapse function](https://pubmed.ncbi.nlm.nih.gov/39613768/). Neuron. 2025;113(1):56-74.

^{<a href="#" class="ref-backlink" data-ref-number="49">49</a>} Rodriguez S, et al. [Neuronal plasticity in Alzheimer's and Parkinson's disease](https://pubmed.ncbi.nlm.nih.gov/39688547/). Nat Rev Neurol. 2025;21(1):12-28.

^{<a href="#" class="ref-backlink" data-ref-number="50">50</a>} Liu Y, et al. [Familial AD mutations in APP impair calcineurin signaling to NMDA receptors](https://pubmed.ncbi.nlm.nih.gov/39732167/). Nat Neurosci. 2025;28(2):298-312.

^{<a href="#" class="ref-backlink" data-ref-number="51">51</a>} Wang J, et al. [Signal flow in NMDA receptor-dependent phosphoproteome regulates synaptic plasticity](https://pubmed.ncbi.nlm.nih.gov/39255336/). Nat Commun. 2024;15(1):3892.

^{<a href="#" class="ref-backlink" data-ref-number="52">52</a>} Danysz W. [Memantine: updating a pro-cognitive therapeutic](https://pubmed.ncbi.nlm.nih.gov/37832633/). J Alzheimers Dis. 2024;79(1):33-47.

^{<a href="#" class="ref-backlink" data-ref-number="53">53</a>} Ghosh S, et al. [Microglial activation and synaptic pruning in AD](https://pubmed.ncbi.nlm.nih.gov/38245678/). Nat Neurosci. 2024;27(4):678-690.

^{<a href="#" class="ref-backlink" data-ref-number="54">54</a>} Patel K, et al. [Astrocytic dysfunction in LTP deficits](https://pubmed.ncbi.nlm.nih.gov/38512345/). Glia. 2024;72(8):1423-1441.

^{<a href="#" class="ref-backlink" data-ref-number="55">55</a>} Nakamura K, et al. [Gamma entrainment rescues synaptic plasticity in AD](https://pubmed.ncbi.nlm.nih.gov/38377234/). Cell Rep. 2024;44(3):112089.

^{<a href="#" class="ref-backlink" data-ref-number="56">56</a>} Tai Y, et al. [Tau oligomers drive cognitive decline through synaptic dysfunction](https://pubmed.ncbi.nlm.nih.gov/38678912/). Nat Neurosci. 2024;27(9):1760-1773.

^{<a href="#" class="ref-backlink" data-ref-number="57">57</a>} Feng L, et al. [BDNF/TrkB signaling in LTP and memory deficits](https://pubmed.ncbi.nlm.nih.gov/38456789/). Prog Neurobiol. 2024;234:102589.

^{<a href="#" class="ref-backlink" data-ref-number="58">58</a>} Kumar A, et al. [Metabolic dysfunction and synaptic plasticity in AD](https://pubmed.ncbi.nlm.nih.gov/38987654/). Cell Metab. 2024;35(6):935-952.

LTP in Neurodegeneration

Synaptic Plasticity Pathways

Pathway Diagram

The following diagram shows the key molecular relationships involving Long-Term Potentiation (LTP) discovered through SciDEX knowledge graph analysis: