Clinical and neuropathological correlates of depression in Alzheimer's disease

1992 ◽  
Vol 22 (4) ◽  
pp. 877-884 ◽  
Author(s):  
Hans Förstl ◽  
Alistair Burns ◽  
Philip Luthert ◽  
Nigel Cairns ◽  
Peter Lantos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Age Of Onset ◽  
Neuronal Degeneration ◽  
Cholinergic Neurons ◽  
Organic Substrate ◽  
Basal Nucleus ◽  
Alzheimer Pathology ◽  
Basal Nucleus Of Meynert

SynopsisDepressive symptoms have been reported in patients with mild to moderate Alzheimer's disease (AD). Recent evidence suggests that a noradrenergic deficit originating from neuronal degeneration in brainstem nuclei may represent an organic correlate of these disturbances. We examined the neuropathological changes in the locus coeruleus (LC), substantia nigra (SN), basal nucleus of Meynert and cortex of 52 patients (12 male, 40 female, mean age 83·2 ± 6·4 years) with pathologically verified AD. Fourteen patients (1 male, 13 female) showed signs of depression. The majority of these patients suffered from severe physical disability or sensory impairment and developed persistent delusions, but had less cognitive impairment. Neuronal counts in the LC were significantly lower than in the 38 patients without depression (36·9 ± 14 ·0; 51·4 ± 28·0 neuromelaninpigmented cells per section per nucleus;F= 3·4, df = 1, 50,P= 0·04). Neuron counts were higher in the basal nucleus of Meynert in depressed AD patients and there were no differences of the neuron numbers in the SN. Depression (main effect;F= 4·5,P= 0·04) contributed significantly to the variance of neuronal counts in the LC, even when covarying for gender, age of onset, cognitive impairment and cortical Alzheimer pathology. The observed disproportionate loss of noradrenergic and cholinergic neurons in the LC and basal nucleus of Meynert may represent an important organic substrate of depression in AD.

scholarly journals Probiotics Fermentation Technology, a Novel Kefir Product, Ameliorates Cognitive Impairment in Streptozotocin-Induced Sporadic Alzheimer’s Disease in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Nesrine S. El Sayed ◽  
Esraa A. Kandil ◽  
Mamdooh H. Ghoneum
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Gut Microbiota ◽  
Neuronal Degeneration ◽  
Amyloid Plaque ◽  
Dependent Manner ◽  
Insulin Degrading Enzyme ◽  
Beneficial Effects ◽  
Fermentation Technology

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by cognitive impairment. Gut microbiota dysfunction (dysbiosis) is implicated in the pathology of AD and is associated with several detrimental consequences, including neurotransmitter depletion, oxidative stress, inflammation, apoptosis, and insulin resistance, which all contribute to the onset of AD. The objective of this study was to assess the effectiveness of Probiotics Fermentation Technology (PFT), a kefir product, in alleviating AD symptoms via regulation of the gut microbiota using a streptozotocin- (STZ-) induced AD mouse model and to compare its activity with simvastatin, which has been proven to effectively treat AD. Mice received one intracerebroventricular injection of STZ (3 mg/kg). PFT (100, 300, 600 mg/kg) and simvastatin (20 mg/kg) were administered orally for 3 weeks. PFT supplementation mitigated STZ-induced neuronal degeneration in the cortex and hippocampus, restored hippocampal acetylcholine levels, and improved cognition in a dose-dependent manner. These effects were accompanied by reductions in oxidative damage, proinflammatory cytokine expression, apoptosis, and tau hyperphosphorylation. Moreover, PFT hindered amyloid plaque accumulation via the enhancement of insulin-degrading enzyme. These beneficial effects were comparable to those produced by simvastatin. The results suggest that PFT can alleviate AD symptoms by regulating the gut microbiota and by inhibiting AD-related pathological events.

scholarly journals Detection and Prediction of Mild Cognitive Impairment in Alzheimer’s Disease Mice

2020 ◽  
Vol 77 (3) ◽  
pp. 1209-1221
Author(s):  
Surya Prakash Rai ◽  
Pablo Bascuñana ◽  
Mirjam Brackhan ◽  
Markus Krohn ◽  
Luisa Möhle ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Dysfunction ◽  
Age Of Onset ◽  
Amyloid Β ◽  
Current Approach ◽  
Classification Algorithm ◽  
Wild Type

Background: The recent failure of clinical trials to treat Alzheimer’s disease (AD) indicates that the current approach of modifying disease is either wrong or is too late to be efficient. Mild cognitive impairment (MCI) denotes the phase between the preclinical phase and clinical overt dementia. AD mouse models that overexpress human amyloid-β (Aβ) are used to study disease pathogenesis and to conduct drug development/testing. However, there is no direct correlation between the Aβ deposition, the age of onset, and the severity of cognitive dysfunction. Objective: To detect and predict MCI when Aβ plaques start to appear in the hippocampus of an AD mouse. Methods: We trained wild-type and AD mice in a Morris water maze (WM) task with different inter-trial intervals (ITI) at 3 months of age and assessed their WM performance. Additionally, we used a classification algorithm to predict the genotype (APPtg versus wild-type) of an individual mouse from their respective WM data. Results: MCI can be empirically detected using a short-ITI protocol. We show that the ITI modulates the spatial learning of AD mice without affecting the formation of spatial memory. Finally, a simple classification algorithm such as logistic regression on WM data can give an accurate prediction of the cognitive dysfunction of a specific mouse. Conclusion: MCI can be detected as well as predicted simultaneously with the onset of Aβ deposition in the hippocampus in AD mouse model. The mild cognitive impairment prediction can be used for assessing the efficacy of a treatment.

Amyloid-β, tau, and the cholinergic system in Alzheimer’s disease: seeking direction in a tangle of clues

2020 ◽  
Vol 31 (4) ◽  
pp. 391-413 ◽  
Author(s):  
Alireza Majdi ◽  
Saeed Sadigh-Eteghad ◽  
Sepideh Rahigh Aghsan ◽  
Fereshteh Farajdokht ◽  
Seyed Mehdi Vatandoust ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Basal Forebrain ◽  
Cholinergic System ◽  
Amyloid Β ◽  
Cholinergic Neurons ◽  
Clinical Findings ◽  
App Metabolism ◽  
Main Culprit

AbstractThe link between histopathological hallmarks of Alzheimer’s disease (AD), i.e. amyloid plaques, and neurofibrillary tangles, and AD-associated cognitive impairment, has long been established. However, the introduction of interactions between amyloid-beta (Aβ) as well as hyperphosphorylated tau, and the cholinergic system to the territory of descriptive neuropathology has drastically changed this field by adding the theory of synaptic neurotransmission to the toxic pas de deux in AD. Accumulating data show that a multitarget approach involving all amyloid, tau, and cholinergic hypotheses could better explain the evolution of events happening in AD. Various species of both Aβ and tau could be traced in cholinergic neurons of the basal forebrain system early in the course of the disease. These molecules induce degeneration in the neurons of this system. Reciprocally, aberrant cholinergic system modulation promotes changes in amyloid precursor protein (APP) metabolism and tau phosphorylation, resulting in neurotoxicity, neuroinflammation, and neuronal death. Altogether, these changes may better correlate with the clinical findings and cognitive impairment detected in AD patients. Failure of several of Aβ- and tau-related therapies further highlights the need for special attention to molecules that target all of these mentioned pathologic changes. Another noteworthy fact here is that none of the popular hypotheses of AD such as amyloidopathy or tauopathy seem to be responsible for the changes observed in AD alone. Thus, the main culprit should be sought higher in the stream somewhere in APP metabolism or Wnt signaling in the cholinergic system of the basal forebrain. Future studies should target these pathological events.

Evolution of Alzheimer's disease-related cytoskeletal changes in the basal nucleus of Meynert

2000 ◽  
Vol 100 (3) ◽  
pp. 259-269 ◽  
Author(s):  
I. Sassin ◽  
C. Schultz ◽  
D. R. Thal ◽  
U. Rüb ◽  
K. Arai ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Basal Nucleus ◽  
Basal Nucleus Of Meynert

Intraparenchymal NGF Infusions Rescue Degenerating Cholinergic Neurons

2000 ◽  
Vol 9 (5) ◽  
pp. 629-636 ◽  
Author(s):  
Mark H. Tuszynski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Basal Forebrain ◽  
Neuronal Degeneration ◽  
Cholinergic Neurons ◽  
Dependent Manner ◽  
Axonal Sprouting ◽  
Adult Rats ◽  
Basal Forebrain Cholinergic Neurons ◽  
Age Related

Nerve growth factor (NGF) exerts both trophic (cell survival) and tropic (axonal growth-promoting) effects on several neuronal populations. In particular, its robust ability to prevent lesion-induced and spontaneous age-related basal forebrain cholinergic neuronal degeneration, and to promote mnemonic recovery, has suggested its potential use as a therapeutic agent in Alzheimer's disease. When infused intracerebroventricularly, however, NGF is associated with several adverse effects that make this delivery route impractical. The present study examined whether intraparenchymal infusions of NGF adjacent to cholinergic neuronal soma are an effective and well-tolerated means of providing NGF to degenerating cholinergic neurons. Cholinergic neuronal rescue together with axonal sprouting responses and local tissue damage in the brain were assessed in adult rats that underwent complete unilateral fornix transections, followed by intraparenchymal infusions of recombinant human NGF for a 2-week period. Intraparenchymal NGF infusions prevented the degeneration of 94.7 ± 6.6% of basal forebrain cholinergic neurons compared to 21.7 ± 2.6% in vehicle-infused animals (p < 0.0001). Cholinergic axons sprouted toward the intraparenchymal NGF source in an apparent gradient-dependent manner. Glial responses to intraparenchymal infusions were minimal, and no apparent toxic effects of the infusions were observed. Thus, when infused intraparenchymally, NGF rescues basal forebrain cholinergic neurons, alters the topography of axonal sprouting responses, and does not induce adverse affects over a 2-week infusion period. Intraparenchymal NGF delivery merits further study at longer term time points as a means of treating the cholinergic component of neuronal loss in Alzheimer's disease.

scholarly journals Smell identification function in early-onset Alzheimer’s disease and mild cognitive impairment

2018 ◽  
Vol 31 (07) ◽  
pp. 1065-1070 ◽  
Author(s):  
Latha Velayudhan ◽  
Frances Wilson-Morkeh ◽  
Emily Penney ◽  
Amala Jovia Maria Jesu ◽  
Sarah Baillon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Early Onset ◽  
Age Of Onset ◽  
Disease Process ◽  
Convenience Sample ◽  
Early Onset Alzheimer’S Disease ◽  
Smell Identification

ABSTRACTLittle is known about olfactory identification (OI) function in early-onset Alzheimer’s disease (EOAD) and early-onset mild cognitive impairment (eoMCI) with age of onset &lt;65 years. We aimed to study OI in EOAD compared with eoMCI and age-matched healthy controls (HC). Nineteen EOAD subjects with mild to moderate dementia, 17 with eoMCI, and 21 HC recruited as a convenience sample from memory services were assessed for cognition, behavioral symptoms, and activities for daily living. The OI was tested using the University of Pennsylvania smell identification test (UPSIT). EOAD participants performed worse compared with eoMCI and HC on cognitive tests and OI (p &lt; 0.001). Although eoMCI had poorer cognitive scores compared to HC, they were similar in their OI function. OI correlated with attention (r = 0.494, p = 0.031), executive functions (r = 0.508, p = 0.026), and praxis (r = 0.455, p = 0.05) within the EOAD group. OI impairment was significantly associated with the diagnosis of EOAD versus eoMCI, but not with eoMCI when compared with HC. OI could potentially be useful in differentiating EOAD from eoMCI. Studies with late-life MCI patients showing OI impairment relative to HC may be attributed to a different disease process. Independent replication in a larger sample is needed to validate these findings.

Correlative decrease of large neurons in the neostriatum and basal nucleus of Meynert in Alzheimer's disease

1989 ◽  
Vol 504 (2) ◽  
pp. 354-357 ◽  
Author(s):  
Kiyomitsu Oyanagi ◽  
Hitoshi Takahashi ◽  
Koichi Wakabayashi ◽  
Fusahiro Ikuta
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Basal Nucleus ◽  
Basal Nucleus Of Meynert ◽  
Large Neurons
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