Christian Humpel's research while affiliated with University of Innsbruck and other places

Publications (273)

Article
The nucleus basalis of Meynert (nBM) is the major source of cholinergic neurons in the basal forebrain, which require nerve growth factor (NGF) for their survival. Melatonin, a pleiotropic hormone, has been shown to exert neuroprotection in several experimental models, but its effect on nBM neurons is not well known. Thus, the aim of this study is...
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Subarachnoid haemorrhage is a devastating disease and results in neurocognitive deficits and poor functional outcome in a considerable proportion of patients. In this study, we investigated the prognostic value of microtubule-associated tau protein measured in the cerebral microdialysate for long-term functional and neuropsychological outcome in po...
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Pregnancy entails substantial changes in brain structure, primarily reduction in gray matter volume in regions subserving social cognition. Maternal brain size begins to decrease after placental implantation and reaches its minimum at term. Subsequent hypoperfusion of placental tissue and placental dysfunction affect neural remodeling in the matern...
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Alzheimer’s disease (AD) is a severe neurodegenerative brain disorder. The determination of beta-amyloid (Aβ)-40, –42, total tau, and phospho-tau-181 (pTau181) in cerebrospinal fluid (CSF) using Lumipulse technology has been established as biomarkers for AD in recent years. As CSF collection is an invasive procedure, one aims to find biomarkers in...
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Neurodegenerative brain disorders are a major burden in our society, such as Alzheimer´s disease. In order to repair or prevent such diseases, drugs are designed which enter the brain, but the blood-brain barrier limits their entry and the search for alternative pathways is important. Recently, we reported that intranasal delivery of the amyloid-be...
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Tau pathology extends throughout the brain in a prion-like fashion through connected brain regions. However, the details of the underlying mechanisms are incompletely understood. The present study aims to examine the spreading of P301S aggregated tau, a mutation that is implicated in tauopathies, using organotypic slice cultures. Coronal hippocampa...
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Alzheimer´s disease is characterized by hyperphosphorylated tau neurofibrillary tangles and beta-amyloid plaques. Both molecules can be easily measured in human fluids or tissue extracts by immunoassays. However, the different molecular weight species can only be differentiated on Western Blot gels. Analysis of native proteins from polyacrylamide g...
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Ischemic stroke is a severe insult in the brain causing cell death, inflammation, and activation of microglia. Microglia are the immune cells of the brain and play a role in any inflammatory process during neurodegeneration. Microglia are round ameboid and migrate to the lesion site, where they differentiate into ramified forms and activated phagoc...
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Background: Platelets (thrombocytes) are small anuclear cells that play an important role in blood clotting. They are activated and dysfunctional in brain disorders, such as Alzheimer's disease (AD) and depression. Platelets express the amyloid-precursor protein (APP) and release beta-amyloid40 into the blood. Recent evidence reports that platelet...
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The accumulation of α-synuclein (α-syn) in the brain plays a role in synucleinopathies and it is hypothesized to spread in a prion-like fashion between connected brain regions. In the present study, we aim to investigate this spreading in well-characterized sagittal organotypic whole brain slices taken from postnatal wild type (WT) and transgenic m...
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The serpinins are relatively novel peptides generated by proteolytic processing of chro-mogranin A and they are comprised of free serpinin, serpinin-RRG and pGlu-serpinin. In this study, the presence and source of these peptides were studied in the skin. By Western blot analysis, a 40 kDa and a 50 kDa protein containing the sequence of serpinin wer...
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Alzheimer's disease is a severe neurodegenerative disorder of the brain, characterized by beta-amyloid plaques, tau pathology, and cell death of cholinergic neurons, resulting in loss of memory. The reasons for the damage of the cholinergic neurons are not clear, but the nerve growth factor (NGF) is the most potent trophic factor to support the sur...
Chapter
Alzheimer’s disease (AD) is a severe neurodegenerative disorder of the brain characterized by extracellular beta-amyloid plaques, intraneuronal tau inclusions, vascular impairment, inflammation, neurodegeneration, and memory loss. Acetylcholine is the most important neurotransmitter for memory, and cholinergic neurons selectively degenerate in AD,...
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To evaluate changes in concentrations of selected biomarkers, neurotrophic factors, and growth factors in the cerebrospinal fluid during pregnancy. A prospective observational study was conducted in 32 pregnant women undergoing gynecological and obstetrical surgery under spinal anesthesia in a university hospital. Beta-amyloid(1-42) and beta-amyloi...
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The role of platelets in hemostasis and thrombosis has long been recognized, recently their contribution to immunological and inflammatory processes is emerging. Platelets could be the missing link between cardiovascular disease, chronic stress and depressive symptoms. Both physical and mental stressors cause platelet activation reflected by change...
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Introduction: Alzheimer's disease (AD) is a severe neurodegenerative disorder of the brain characterized by degeneration of cholinergic neurons which is directly linked to cognitive decline. Nerve growth factor (NGF) is the most potent protective factor for cholinergic neurons, additionally the NMDA antagonist memantine blocks glutamate-mediated e...
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Alzheimer’s disease (AD) is pathologically characterized by extracellular beta-amyloid (Aβ) plaques and intraneuronal tau tangles in the brain. A therapeutic strategy aims to prevent or clear these Aβ plaques and the Aβ-degrading enzyme neprilysin is a potent drug to degrade plaques. The major challenge is to deliver bioactive neprilysin into the b...
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The extracellular deposition of b-amyloid (Aβ) is one of the major characteristics in Alzheimer´s disease (AD). The”spreading hypothesis” suggests that a pathological protein (similar to prions) spreads over the entire brain. The aim of the present study was to use organotypic brain slices of postnatal day 8–10 mice. Using collagen hydrogels, we ap...
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Objectives In clinical practice it is important to identify patients suffering from mild cognitive impairment (MCI) who will progress to Alzheimer's disease (AD). The purpose of this study is to investigate whether lipid metabolites and vitamin B12 and folate levels are effective biomarker for an accurate prediction of MCI-to-AD conversion. Method...
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Protection or repair of the nigrostriatal pathway represents a principal disease-modifying therapeutic strategy for Parkinson's disease (PD). Glial cell line-derived neurotrophic factor (GDNF) holds great therapeutic potential for PD, but its efficacious delivery remains difficult. The aim of this study was to evaluate the potential of different bi...
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Vessel damage is a general pathological process in many neurodegenerative disorders, as well as spinal cord injury, stroke, or trauma. Biomaterials can present novel tools to repair and regenerate damaged vessels. The aim of the present study is to test collagen hydrogels loaded with different angiogenic factors to study vessel repair in organotypi...
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The understanding and neurological prognostication of hypoxic ischemic encephalopathy (HIE) after hypothermic cardiac arrest (CA) is limited. Recent data suggest that the protein tau (total tau) might be a useful marker for outcome in patients with HIE. This translational porcine study aimed to analyze brain physiology in relation to total tau prot...
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Alzheimer's disease is a severe neurodegenerative brain disorder and characterized by deposition of extracellular toxic β-amyloid (42) plaques and the formation of intracellular tau neurofibrillary tangles. In addition, β-amyloid peptide deposits are found in the walls of small to medium blood vessels termed cerebral amyloid angiopathy (CAA). Howev...
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During pregnancy, substantial alterations in cerebral plasticity, vascular remodeling and neuronal growth occur in the maternal brain. We investigated whether concentrations of selected neurodiagnostic biomarkers in the cerebrospinal fluid of women with preeclampsia/HELLP syndrome differ from those in healthy controls using enzyme-linked immunosorb...
Article
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia worldwide. As age is the main risk factor, > 97% of all AD cases are of sporadic origin, potentiated by various risk factors associated with life style and starting at an age > 60 years. Only < 3% of AD cases are of genetic origin caused by mut...
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Aim: We evaluated serum tau protein as biomarker for poor neurological outcome over an extended observation period in patients after successful cardiopulmonary resuscitation (CPR) treated with mild therapeutic hypothermia (MTH) or normothermia (NT). Methods: This is a retrospective analysis of a prospective observational study including 132 pati...
Article
Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder and the most common form of dementia coming along with cerebral amyloid angiopathy (CAA) in more than 70% of all cases. However, CAA occurs also in pure form without AD pathology. Vascular life style risk factors such as obesity, hypertension, hypercholesterolemia, diabetes,...
Article
Glial cell line-derived neurotrophic factor (GDNF) is a potent trophic factor that supports the survival of dopaminergic neurons of the substantia nigra (SN), which degenerate in Parkinson's disease (PD). The application of GDNF to the brain is challenging but biomaterials such as collagen can present novel strategies to target therapeutics to the...
Article
Diagnosis of Alzheimer's disease (AD) is still a challenge. Salivary analysis could produce an easily accessible and inexpensive possibility to study metabolic changes in AD. In the present pilot study, we show for the first time using targeted metabolomics that acyl-alkyl phosphatidylcholines (PCae C34:1-2; Pcae C36:1-2-3; PcaeC38:1c3; Pcae C40:2-...
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Transgenic mice have been extensively used to study the Alzheimer pathology. In order to reduce, refine and replace (3Rs) the number of animals, ex vivo cultures are used and optimized. Organotypic brain slices are the most potent ex vivo slice culture models, keeping the 3-dimensional structure of the brain and being closest to the in vivo situati...
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Abstract Platelets are anuclear blood cells and play a major role in hemostasis and thrombosis. Platelets express amyloid-precursor protein (APP), release beta-amyloid (Aβ) and are stimulated (pre-activated) in Alzheimer’s disease (AD). We hypothesize that such stimulated platelets severely damage brain vessels which subsequently leads to cerebrova...
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Ex vivo cell culture models are of particular interest for neurobiologists, as these allow the study of brain cells in an isolated environment. Organotypic brain slice cultures allow growth of three‐dimensional brain tissue that conserves the cellular architecture. This unit describes the preparation and culturing of organotypic brain slices from m...
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In patients with aneurysmal subarachnoid hemorrhage (aSAH), increased brain extracellular interleukin (IL)-6 levels measured by cerebral microdialysis (CMD) were associated with disease severity, early brain injury, delayed cerebral infarction, and axonal injury. In this study, we analyzed brain extracellular IL-6 levels of aSAH patients following...
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Alzheimer's disease (AD) is characterized by amyloid-β plaques, tau pathology and vascular impairment including pericyte damage. Pericytes are perivascular cells of the blood-brain barrier and can differentiate into different cell types in vitro including microglia. The aim of the present study is to explore if primary mouse brain pericytes isolate...
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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder of the brain, characterized by extracellular aggregation of beta-amyloid (Aβ) and hyperphosphorylation of tau causing intraneuronal neurofibrillary tangles (NFTs). There is urgent need to study the interactions between Aβ and tau, especially to solve the question of the pathologic...
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Biomaterials have increasingly become a focus of research on neuroprotection and neuroregeneration. Collagen, in terms of brain repair, presents many advantages such as being remarkably biocompatible, biodegradable, versatile and non-toxic. Collagen can be used to form injectable scaffolds and micro/nano spheres in order to: (i) locally release the...
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Background: Alzheimeŕs disease is accompanied by cell death of cholinergic neurons, resulting in cognitive impairment and memory loss. Nerve growth factor (NGF) is the most potent protein to support survival of cholinergic neurons. New METHOD: Organotypic brain slices of the basal nucleus of Meynert (nBM) are a valuable tool to study cell death of...
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Introduction There is still a clear need for a widely available, inexpensive and reliable method to diagnose Alzheimer’s disease (AD) and monitor disease progression. Liquid chromatography–mass spectrometry (LC-MS) is a powerful analytic technique with a very high sensitivity and specificity. Objectives The aim of the present study is to measure c...
Article
Alzheimer´s disease (AD) is a severe neurodegenerative brain disorder characterized by beta-amyloid plaques, Tau pathology, inflammation, neurodegeneration, and cerebrovascular dysfunction. Besides that, alterations in monocytes and platelets have been reported in the blood of Alzheimer patients. In the present study, we measured circulating levels...
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Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) can be supported by the analysis of Tau and 14-3-3 in the cerebrospinal fluid (CSF). In this short report, we report about a retrospective analysis performed on 2,296 routinely collected CSF samples, and 44 samples with a ratio of phosphoTau181/Tau <0.075 were selected. Analysis was performed wi...
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Background: Alzheimer's disease is a severe neurodegenerative brain disorder, showing severe beta-amyloid depositions in the brain (plaques) and in vessels (cerebral amyloid angiopathy, CAA), tau pathology, neurodegeneration (and loss of acetylcholine), inflammation with reactive astrocytes and microglia and cerebrovascular damage, all resulting i...
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Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the central nervous system. The use of biological fluids in AD diagnosis remains limited to the analysis of specific protein biomarkers in cerebrospinal fluid. However, metabolomic analysis has recently revealed several metabolites in plasma, especially phosphatidylcholines (PC...
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Alzheimer?s disease (AD) is a chronic neurodegenerative disorder that is mainly characterized by beta-amyloid (A?) plaque deposition, Tau pathology and dysfunction of the cholinergic system causing memory impairment. The aim of the present study was to examine (1) anxiety and cognition, (2) A? plaque deposition and (3) degeneration of cholinergic n...
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Objectives: During pregnancy various interactions occur between structural alterations of the maternal brain and placental metabolism. The aim of the present study was to investigate whether cerebrospinal fluid concentrations of tau and phospho-tau-181 protein vary during normal pregnancy and in women with preeclampsia and HELLP syndrome. Study d...
Article
Alzheimer's disease (AD) is a severe neurodegenerative disorder of the brain, characterized by extracellular beta-amyloid (Aβ) plaques, intracellular tau pathology, neurodegeneration and inflammation. There is clear evidence that the blood-brain barrier is damaged in AD and that vessel function is impaired. Alpha-smooth muscle actin (αSMA) is a pro...
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Strong evidence shows an association between cerebral vascular diseases and Alzheimer´s disease (AD). In order to study the interaction of beta-amyloid (Aβ) plaques with brain vessels, we crossbred an AD mouse model (overexpressing amyloid precursor protein with the Swedish-Dutch-Iowa mutations, APP_SweDI) with mice expressing green fluorescent pro...
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Alzheimer’s disease (AD) is pathologically characterized by beta-amyloid (Aβ) plaques and Tau pathology. It is well-established that Aβ plaques are surrounded by reactive astrocytes, highly expressing glial fibrillary acidic protein (GFAP). In order to study the cellular interaction of reactive astrocytes with Aβ plaques, we crossbred mice overexpr...
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Pericytes are perivascular cells and have heterogenous roles in the brain, such as controlling blood flow and entry of immune cells or regulating the blood-brain barrier. Platelet-derived growth factor (PDGF) receptor-beta (PDGFRβ) is highly expressed in pericytes, representing the most selective biomarker. The aim of the present study was to cultu...
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Introduction: Animal data suggest an association between neuroinflammation and secondary brain injury including axonal injury after aneurysmal subarachnoid hemorrhage (aSAH). We sought to study the association between brain extracellular interleukin (IL)-6 and TAU-protein levels as a surrogate marker for neuroinflammation and axonal injury in pati...
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There is a substantial amount of evidence from animal models that early brain injury (EBI) may play an important role for secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Cerebral microdialysis (CMD) allows online measurement of brain metabolites including the pro-inflammatory-cytokine interleukin-6 (IL-6) and matrix-metallop...
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Brain vessels are the most important structures in the brain to deliver energy and substrates to neurons. Brain vessels are composed of a complex interaction between endothelial cells, pericytes, and astrocytes, controlling the entry of substrates into the brain. Damage of brain vessels and vascular impairment are general pathologies observed in di...
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In vitro cell cultures are an important tool for obtaining insights into cellular processes in an isolated system and a supplement to in vivo animal experiments. While primary dissociated cultures permit a single homogeneous cell population to be studied, there is a clear need to explore the function of brain cells in a threee-dimensional system wh...
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Platelets are important in hemostasis, but also contain adhesion molecules, pro-inflammatory and immune-modulatory compounds, as well as most of the serotonin outside the central nervous system. Dysbalance in the serotonin pathways is involved in the pathogenesis of depressive symptoms. Thus, changes in platelet aggregation and content of bioactive...
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid-β (Aβ) plaque formation, tau pathology, neurodegeneration and inflammatory processes. Monocytes are involved in inflammation in AD and are recruited to the diseased brain. Recently it has been shown that aberrant epigenetic processes including acetylation are associat...
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Background: Metabolomic processes have been identified as being strongly linked to the development of Alzheimer's disease (AD). Thus, lipid metabolites appear to be highly useful as diagnostic substrates for the diagnosis of AD and mild cognitive impairment (MCI) in plasma. Methods: We analyzed plasma samples from controls (n = 35), MCI (n = 33)...
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Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized mainly by accumulation of amyloid-β plaques and neurofibrillary tangles, synaptic and neuronal loss. Blood platelets contain the neurotransmitter serotonin and amyloid-precursor protein (APP), and may thus be useful as a peripheral biomarker for AD. The aim of the present...
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Alzheimer´s disease is a severe neurodegenerative disorder of the brain, pathologically characterized by extracellular beta-amyloid plaques, intraneuronal Tau inclusions, inflammation, reactive glial cells, vascular pathology and neuronal cell death. The degradation and clearance of beta-amyloid plaques is an interesting therapeutic approach, and t...
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Alzheimer's disease (AD) is characterized by the deposition of β-amyloid (Aβ) senile plaques and tau-associated neurofibrillary tangles. Other disease features include neuroinflammation and cholinergic neurodegeneration, indicating their possible importance in disease propagation. Recent studies have shown that monocytic cells can migrate into the...
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Alzheimer's disease (AD) is a neurodegenerative disease that leads to the progressive deterioration of cognitive and memory function. The deposition of extracellular beta-amyloid (Aβ) senile plaques and intracellular tau neurofibrillary tangles are considered the cardinal pathological hallmarks of AD, however, accumulating evidence indicates that i...
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Background Changes in platelet bioactivity and aggregation are of interest when studying patients with depression as this could help to explain the statistically observed association of depression and chronic somatic, especially cardiovascular disease. This link could potentially be mediated through serotonergic signaling or immunological changes....
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Alzheimer's disease (AD) is characterized by extracellular beta-amyloid plaques and intracellular tau tangles. AD-related pathology is often accompanied by vascular changes. The predominant vascular lesions in AD are cerebral amyloid angiopathy (CAA) and arteriosclerosis. Platelets circulate along the vessel wall responding immediately to vascular...
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It is well established that L-type calcium channels (LTCC) are expressed in astroglia. However, their functional role is still speculative, especially under pathological conditions. We recently showed that the α1 subunit-like immunoreactivity of the CaV1.2 channel is strongly expressed in reactive astrocytes around beta-amyloid plaques in 11-month-...
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Alzheimer's disease (AD) is a severe and chronic neurodegenerative disorder of the brain. The laboratory diagnosis is limited to the analysis of three biomarkers in cerebrospinal fluid (CSF): amyloid-β42 (Aβ42), total tau, and phospho-tau-181 (P-tau-181). However, there is a need to find more biomarkers in CSF that can improve the sensitivity and s...
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Triple Tg-AD mice display an AD-like pathology at 20 months of age.•No microbleedings are seen but ventricle size is enlarged.•Cholesterol-fed 3xTg-AD mice do not survive past 14 months of age.•Cholesterol does not markedly potentiate AD-like pathology.•Cholesterol increases stress-related plasma corticosterone.•Cholesterol affects brain vessel pat...
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We have generated a novel, neuro-specific ncRNA microarray, covering 1472 ncRNA species, to investigate their expression in different mouse models for central nervous system diseases. Thereby, we analyzed ncRNA expression in two mouse models with impaired calcium channel activity, implicated in Epilepsy or Parkinson's disease, respectively, as well...
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Neurodegeneration of cholinergic and dopaminergic neurons is a major hallmark in Alzheimer's or Parkinson's disease, respectively. A dysregulation in calcium homeostasis may be part of this process and counteracting calcium influx may have neuroprotective properties in both diseases. Therefore, we investigated the putative neuroprotective or neurot...
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Background: Spontaneous intracerebral hemorrhage (ICH) is associated with high morbidity and mortality. Cortical spreading depolarizations (CSDs) increase brain matrix metalloproteinase (MMP)-9 activity leading to perihematomal edema expansion in experimental ICH. Methods: The purpose of this report is to describe cerebral metabolic changes and...
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Platelets play a role in repair of vessels and contain different growth factors, including nerve growth factor (NGF). Since NGF is the most potent growth factor to support survival of cholinergic neurons, we aimed to study the effects of platelet-derived NGF on cholinergic neurons in organotypic brain slices. Brain slices of the nucleus basalis of...
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Recent evidence suggests axonal injury after aneurysmal subarachnoid haemorrhage (aSAH). The microtubule-associated protein, tau, has been shown to be elevated in the cerebrospinal fluid after aSAH, however, brain extracellular tau levels and their relation to long-term neurological and cognitive outcomes have not been investigated. Serial cerebral...
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The recruitment of monocytes into the brain has been implicated in Alzheimer's disease and recent studies have indicated that monocytes can reduce amyloid plaque burden. Our previous investigations have shown that hypercholesterolemic rats develop cognitive, cholinergic, and blood-brain barrier dysfunction, but do not develop amyloid plaques. This...
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Background: It is well established that reactive astrocytes express L-type calcium channels (LTCC), but their functional role is completely unknown. We have recently shown that reactive astrocytes highly express the CaV1.2 α1-subunit around β-amyloid (Aβ) plaques in an Alzheimer mouse model. The aim of the present study was to explore whether Aβ p...
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Alzheimer´s disease (AD) is a severe neurodegenerative disease. Cerebrovascular changes often accompany AD-related pathology. Despite a considerable progress in the diagnostic accuracy of AD, no blood biomarkers have been established so far. The aim of the present study was to search for changes in plasma levels of 27 vascular-related proteins of h...
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Flavonoids target a variety of pathophysiological mechanisms and are therefore increasingly considered as compounds encompassed with therapeutic potentials in diseases such as cancer, diabetes, arteriosclerosis, and neurodegenerative diseases and mood disorders. Hops (Humulus lupulus L.) is rich in flavonoids such as the flavanone 8-prenylnaringeni...
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A variety of cardiovascular and cerebrovascular diseases are associated with alterations in cholesterol levels and metabolism. Moreover, convincing evidence shows that high cholesterol diet can lead to learning and memory impairments. On the other hand, a significant body of research has also demonstrated that learning is improved by elevated dieta...
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A marker of Alzheimer's disease (AD) with a high sensitivity and specificity would facilitate a diagnosis at early stages. Blood platelets may be of particular interest in search of biomarkers, because they express amyloid-precursor protein (APP), and display a dysfunctional processing in AD. The aim of the present study is to establish and validat...
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Increased activity of L-type Ca2+ channels has been implicated in the pathogenesis of dementia and Alzheimer's disease (AD). Previously we detected CaV1.2 α1-subunit-positive expression in reactive astrocytes surrounding the plaques of 12 month-old transgenic mice overexpressing hAβPP751 with the London (V717I) and Swedish (K670M/N671L) mutations....
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It remains unclear whether monocyte infiltration plays a protective or detrimental role in neurodegenerative disease. The present study characterizes the inflammatory status of primary monocytes in a novel in vitro perfusion model. Monocytes under perfusion do not undergo elevated cell death. However, perfusion does lead to altered morphology, whic...
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Nerve growth factor (NGF), a member of the neurotrophin family, is responsible for the maintenance and survival of cholinergic neurons in the basal forebrain. The degeneration of cholinergic neurons and reduced acetycholine levels are hallmarks of Alzheimer's disease (AD) as well as associated with learning and memory deficits. Thus far, NGF has pr...