scholarly journals Reduction of Basal Forebrain Cholinergic System Parallels Cognitive Impairment in Patients at High Risk of Developing Alzheimer's Disease

2009 ◽  
Vol 20 (7) ◽  
pp. 1685-1695 ◽  
Author(s):  
M. Grothe ◽  
L. Zaborszky ◽  
M. Atienza ◽  
E. Gil-Neciga ◽  
R. Rodriguez-Romero ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
High Risk ◽  
Basal Forebrain ◽  
Cholinergic System

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.

The Functional Organization of the Basal Forebrain Cholinergic System in Primates and the Role of this System in Alzheimer's Disease

1985 ◽  
Vol 444 (1 Memory Dysfun) ◽  
pp. 287-295 ◽  
Author(s):  
DONALD L. PRICE ◽  
LINDA C. CORK ◽  
ROBERT G. STRUBLE ◽  
PETER J. WHITEHOUSE ◽  
CHERYL A. KITT ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Basal Forebrain ◽  
Cholinergic System ◽  
Functional Organization

IC-P-105: Basal forebrain and hippocampus as predictors of conversion to Alzheimer's disease in patients with mild cognitive impairment: A multicenter DTI and volumetry study

2015 ◽  
Vol 11 (7S_Part_2) ◽  
pp. P72-P72
Author(s):  
Katharina Brüggen ◽  
Martin Dyrba ◽  
Frederik Barkhof ◽  
Lucrezia Hausner ◽  
Massimo Filippi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Basal Forebrain

Aging, Alzheimer's disease, and the cholinergic system of the basal forebrain

Neurology ◽  
1984 ◽  
Vol 34 (6) ◽  
pp. 741-741 ◽  
Author(s):  
P. L. McGeer ◽  
E. G. McGeer ◽  
J. Suzuki ◽  
C. E. Dolman ◽  
T. Nagai
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Basal Forebrain ◽  
Cholinergic System

Loss of basal forebrain P75NTR immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease

2002 ◽  
Vol 443 (2) ◽  
pp. 136-153 ◽  
Author(s):  
Elliott J. Mufson ◽  
Shuang Y. Ma ◽  
John Dills ◽  
Elizabeth J. Cochran ◽  
Sue Leurgans ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Basal Forebrain

The 12th J. A. F. Stevenson Memorial Lecture: Aging, Alzheimer's disease, and the cholinergic system

1984 ◽  
Vol 62 (7) ◽  
pp. 741-754 ◽  
Author(s):  
Patrick L. McGeer
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Substantia Nigra ◽  
Locus Coeruleus ◽  
Basal Forebrain ◽  
Cholinergic System ◽  
Memory Storage ◽  
Substantia Nigra Pars Compacta ◽  
Memorial Lecture ◽  
Reticular Activating System

Aging does not affect tissues in a uniform fashion. Within the brain, substantial neuronal dropout occurs with age in the cholinergic medial basal forebrain complex, the noradrenergic locus coeruleus, and the dopaminergic substantia nigra pars compacta. These areas are also struck by diseases that are sharply age dependent. Alzheimer's disease causes neuronal destruction in the cholinergic cells of the medial basal forebrain and noradrenergic cells of the locus coeruleus. Parkinson's disease causes neuronal destruction mainly in the substantia nigra but with some destruction in the locus coeruleus. Parkinsonism–dementia affects all three areas. Alzheimer's disease is responsible for 50–60% of all cases of dementia. Severe dementia rises in frequency from less than 1% of the population at age 65–70 to over 15% by age 85. The cause of the disease is unknown. No method of prevention is known and present treatments are ineffective, although modest improvement has been reported for various therapeutic regimens designed to stimulate the cholinergic system. The neuronal systems identified as being affected in Alzheimer's disease and in the dementia of Parkinsonism correspond with those shown many years ago to be associated with the reticular activating system. This correspondence permits a new hypothesis of cognition and memory to be put forward, as well as a reinterpretation of data from animal research on the reticular activating system performed over a quarter of a century ago. The locus coeruleus is proposed as the noradrenergic element sensitizing the cortex to conscious recognition of real time events. The medial basal forebrain complex is proposed as the system registering the conscious event for storage and as the readout device when it is subsequently redisplayed in the cortex as memory. Storage could either be in the temporal lobe, in several areas of cortex with feedback to the medial basal forebrain, or in the cholinergic cells themselves.

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