Abstract
Recent evidence indicates that the nucleus basalis of Meynert, a distinct population of basal forebrain neurons, is a major source of cholinergic innervation of the cerebral cortex. Postmortem studies have previously demonstrated profound reduction in the presynaptic markers for cholinergic neurons in the cortex of patients with Alzheimer's disease and senile dementia of the Alzheimer's type. The results of this study show that neurons of the nucleus basalis of Meynert undergo a profound (> 75 percent) and selective degeneration in these patients and provide a pathological substrate of the cholinergic deficiency in their brains. Demonstration of selective degeneration of such neurons represents the first documentation of a loss of a transmitter-specific neuronal population in a major disorder of higher cortical function and, as such, points to a critical subcortical lesion in Alzheimer's patients.
References
53
Referenced
2,898
-
AMARAL, D. G., JOURNAL OF COMPARATIVE NEUROLOGY 189: 573 (1980).
(
10.1002/cne.901890402
) / JOURNAL OF COMPARATIVE NEUROLOGY (1980) -
BECKSTEAD, R.M., AFFERENT CONNECTIONS OF ENTORHINAL AREA IN RAT AS DEMONSTRATED BY RETROGRADE CELL-LABELING WITH HORSERADISH-PEROXIDASE, BRAIN RESEARCH 152: 249 (1978).
(
10.1016/0006-8993(78)90254-8
) / BRAIN RESEARCH (1978) - Brody, H., Alzheimer's Disease: Senile Dementia and Related Disorders 7: 345 (1978). / Alzheimer's Disease: Senile Dementia and Related Disorders (1978)
-
BRODY, H, ORGANIZATION OF THE CEREBRAL CORTEX .3. A STUDY OF AGING IN THE HUMAN CEREBRAL CORTEX, JOURNAL OF COMPARATIVE NEUROLOGY 102: 511 (1955).
(
10.1002/cne.901020206
) / JOURNAL OF COMPARATIVE NEUROLOGY (1955) -
COLON, E.J., CEREBRAL-CORTEX IN PRESENILE DEMENTIA - QUANTITATIVE-ANALYSIS, ACTA NEUROPATHOLOGICA 23: 281 (1973).
(
10.1007/BF00687457
) / ACTA NEUROPATHOLOGICA (1973) -
CONRAD, LCA, CONNECTIONS OF MEDIAN AND DORSAL RAPHE NUCLEI IN RAT - AUTORADIOGRAPHIC AND DEGENERATION STUDY, JOURNAL OF COMPARATIVE NEUROLOGY 156: 179 (1974).
(
10.1002/cne.901560205
) / JOURNAL OF COMPARATIVE NEUROLOGY (1974) - Coyle, J. T., Brain Neurotransmitters and Receptors in Aging and Age-Related Disorders: 149 (1981). / Brain Neurotransmitters and Receptors in Aging and Age-Related Disorders (1981)
- DAVIES P COMMUNICATION.
- DAVIES, P, SELECTIVE LOSS OF CENTRAL CHOLINERGIC NEURONS IN ALZHEIMERS-DISEASE, LANCET 2: 1403 (1976). / LANCET (1976)
- DAVIS, K.L., BRAIN ACETYLCHOLINE: 205 (1979). / BRAIN ACETYLCHOLINE (1979)
10.1152/jn.1971.34.3.414
-
DIVAC, I, MAGNOCELLULAR NUCLEI OF BASAL FOREBRAIN PROJECT TO NEOCORTEX, BRAIN-STEM, AND OLFACTORY BULB - REVIEW OF SOME FUNCTIONAL CORRELATES, BRAIN RESEARCH 93: 385 (1975).
(
10.1016/0006-8993(75)90178-X
) / BRAIN RESEARCH (1975) - DRACHMAN, D.A., AGING 7: 141 (1978). / AGING (1978)
-
GORRY, J.D., STUDIES ON COMPARATIVE ANATOMY OF GANGLION BASALE OF MEYNERT, ACTA ANATOMICA 55: 51 (1963).
(
10.1159/000142464
) / ACTA ANATOMICA (1963) - GUILLERY, R.W., AFFERENT FIBRES TO THE DORSO-MEDIAL THALAMIC NUCLEUS IN THE CAT, JOURNAL OF ANATOMY 93: 403 (1959). / JOURNAL OF ANATOMY (1959)
- HASSLER, R, BEHAV AGING NERVOUS: 284 (1965). / BEHAV AGING NERVOUS (1965)
-
HENDERSON, G, CELL COUNTS IN HUMAN CEREBRAL-CORTEX IN NORMAL ADULTS THROUGHOUT LIFE USING AN IMAGE ANALYZING COMPUTER, JOURNAL OF THE NEUROLOGICAL SCIENCES 46: 113 (1980).
(
10.1016/0022-510X(80)90048-9
) / JOURNAL OF THE NEUROLOGICAL SCIENCES (1980) - JOHNSTON, M.V., EVIDENCE FOR A CHOLINERGIC PROJECTION TO NEOCORTEX FROM NEURONS IN BASAL FOREBRAIN, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 76: 5392 (1979). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1979)
-
JONES, E.G., MIDBRAIN, DIENCEPHALIC AND CORTICAL RELATIONSHIPS OF BASAL NUCLEUS OF MEYNERT AND ASSOCIATED STRUCTURES IN PRIMATES, JOURNAL OF COMPARATIVE NEUROLOGY 167: 385 (1976).
(
10.1002/cne.901670402
) / JOURNAL OF COMPARATIVE NEUROLOGY (1976) -
KATZMAN, R, PREVALENCE AND MALIGNANCY OF ALZHEIMER-DISEASE - MAJOR KILLER, ARCHIVES OF NEUROLOGY 33: 217 (1976).
(
10.1001/archneur.1976.00500040001001
) / ARCHIVES OF NEUROLOGY (1976) 10.1126/science.1114317
-
KRETTEK, J.E., AMYGDALOID PROJECTIONS TO SUB-CORTICAL STRUCTURES WITHIN BASAL FOREBRAIN AND BRAIN-STEM IN RAT AND CAT, JOURNAL OF COMPARATIVE NEUROLOGY 178: 225 (1978).
(
10.1002/cne.901780204
) / JOURNAL OF COMPARATIVE NEUROLOGY (1978) - KRNJEVIC, K, A HISTOCHEMICAL STUDY OF CHOLINERGIC FIBRES IN CEREBRAL CORTEX, JOURNAL OF ANATOMY 99: 711 (1965). / JOURNAL OF ANATOMY (1965)
- KUHAR, M.J., BIOL CHOLINERGIC FUN: 3 (1976). / BIOL CHOLINERGIC FUN (1976)
-
LEHMANN, J, THE NUCLEUS BASALIS-MAGNOCELLULARIS - THE ORIGIN OF A CHOLINERGIC PROJECTION TO THE NEOCORTEX OF THE RAT, NEUROSCIENCE 5: 1161 (1980).
(
10.1016/0306-4522(80)90195-5
) / NEUROSCIENCE (1980) - LYNCH, G, DIRECT PROJECTIONS FROM BRAIN-STEM TO TELENCEPHALON, EXPERIMENTAL BRAIN RESEARCH 17: 221 (1973). / EXPERIMENTAL BRAIN RESEARCH (1973)
- MCKINNEY M unpublished data.
-
MESULAM, M.M., ACETYLCHOLINESTERASE-RICH PROJECTIONS FROM BASAL FOREBRAIN OF RHESUS-MONKEY TO NEOCORTEX, BRAIN RESEARCH 109: 152 (1976).
(
10.1016/0006-8993(76)90385-1
) / BRAIN RESEARCH (1976) - MEYNERT T STRICKERS HDB LEHRE (1872).
-
MIZUNO, N, FIBER PROJECTIONS FROM ROSTRAL BASAL FOREBRAIN STRUCTURES IN CAT, EXPERIMENTAL NEUROLOGY 25: 220 (1969).
(
10.1016/0014-4886(69)90046-6
) / EXPERIMENTAL NEUROLOGY (1969) -
NAUTA, WJH, HIPPOCAMPAL PROJECTIONS AND RELATED NEURAL PATHWAYS TO THE MID-BRAIN IN THE CAT, BRAIN 81: 319 (1958).
(
10.1093/brain/81.3.319
) / BRAIN (1958) -
NORITE, M, SUB-CORTICAL AFFERENTS TO THE MONKEY AMYGDALA - AN HRP STUDY, BRAIN RESEARCH 190: 225 (1980).
(
10.1016/0006-8993(80)91171-3
) / BRAIN RESEARCH (1980) -
OTTERSEN, O.P., AFFERENT CONNECTIONS TO THE AMYGDALOID COMPLEX OF THE RAT AND CAT .2. AFFERENTS FROM THE HYPOTHALAMUS AND THE BASAL TELENCEPHALON, JOURNAL OF COMPARATIVE NEUROLOGY 194: 267 (1980).
(
10.1002/cne.901940113
) / JOURNAL OF COMPARATIVE NEUROLOGY (1980) - PARENT, A, ADVANCES IN NEUROLOGY 24: 1 (1979). / ADVANCES IN NEUROLOGY (1979)
-
PARENT, A, MORPHOLOGICAL-CHARACTERISTICS OF ACETYLCHOLINESTERASE-CONTAINING NEURONS IN CNS OF DFP-TREATED MONKEYS .2. DIENCEPHALIC AND MEDIAL TELENCEPHALIC STRUCTURES, JOURNAL OF THE NEUROLOGICAL SCIENCES 32: 9 (1977).
(
10.1016/0022-510X(77)90036-3
) / JOURNAL OF THE NEUROLOGICAL SCIENCES (1977) -
PERRY, E.K., NEUROTRANSMITTER ENZYME ABNORMALITIES IN SENILE DEMENTIA - CHOLINE-ACETYLTRANSFERASE AND GLUTAMIC-ACID DECARBOXYLASE ACTIVITIES IN NECROPSY BRAIN-TISSUE, JOURNAL OF THE NEUROLOGICAL SCIENCES 34: 247 (1977).
(
10.1016/0022-510X(77)90073-9
) / JOURNAL OF THE NEUROLOGICAL SCIENCES (1977) - PRICE, J.L., AFFERENT CONNEXIONS OF NUCLEUS OF HORIZONTAL LIMB OF DIAGONAL BAND, JOURNAL OF ANATOMY 107: 239 (1970). / JOURNAL OF ANATOMY (1970)
-
REISINE, T.D., PRESYNAPTIC AND POSTSYNAPTIC NEUROCHEMICAL ALTERATIONS IN ALZHEIMERS-DISEASE, BRAIN RESEARCH 159: 477 (1978).
(
10.1016/0006-8993(78)90562-0
) / BRAIN RESEARCH (1978) -
SEGAL, M, AFFERENTS TO HIPPOCAMPUS OF RAT STUDIED WITH METHOD OF RETROGRADE TRANSPORT OF HORSERADISH-PEROXIDASE, BRAIN RESEARCH 78: 1 (1974).
(
10.1016/0006-8993(74)90349-7
) / BRAIN RESEARCH (1974) -
SEGAL, M, AFFERENTS TO ENTORHINAL CORTEX OF RAT STUDIED BY METHOD OF RETROGRADE TRANSPORT OF HORSERADISH-PEROXIDASE, EXPERIMENTAL NEUROLOGY 57: 750 (1977).
(
10.1016/0014-4886(77)90106-6
) / EXPERIMENTAL NEUROLOGY (1977) -
SHUTE, CCD, ASCENDING CHOLINERGIC RETICULAR SYSTEM - NEOCORTICAL OLFACTORY AND SUBCORTICAL PROJECTIONS, BRAIN 90: 497 (1967).
(
10.1093/brain/90.3.497
) / BRAIN (1967) -
SMITH, C.M., POSSIBLE BIOCHEMICAL BASIS OF MEMORY DISORDER IN ALZHEIMER-DISEASE, ANNALS OF NEUROLOGY 3: 471 (1978).
(
10.1002/ana.410030602
) / ANNALS OF NEUROLOGY (1978) -
SWANSON, L.W., CONNECTIONS OF THE SEPTAL REGION IN THE RAT, JOURNAL OF COMPARATIVE NEUROLOGY 186: 621 (1979).
(
10.1002/cne.901860408
) / JOURNAL OF COMPARATIVE NEUROLOGY (1979) -
Terry, R. D., Annals of Neurology 10: 184 (1981).
(
10.1002/ana.410100209
) / Annals of Neurology (1981) -
TERRY, R.D., DEMENTIA OF THE ALZHEIMER TYPE, ANNUAL REVIEW OF NEUROSCIENCE 3: 77 (1980).
(
10.1146/annurev.ne.03.030180.000453
) / ANNUAL REVIEW OF NEUROSCIENCE (1980) - TOMLINSON, B.E., DEMENTIA: 113 (1977). / DEMENTIA (1977)
- WANG, H, AGING DEMENTIA: 1 (1977). / AGING DEMENTIA (1977)
- WANG, H.S., REPORT PANEL INFLAMM: 61 (1979). / REPORT PANEL INFLAMM (1979)
-
WENK, H, CHOLINERGIC PROJECTIONS FROM MAGNOCELLULAR NUCLEI OF THE BASAL FOREBRAIN TO CORTICAL AREAS IN RATS, BRAIN RESEARCH REVIEWS 2: 295 (1980).
(
10.1016/0165-0173(80)90011-9
) / BRAIN RESEARCH REVIEWS (1980) - WHITE, P, NEOCORTICAL CHOLINERGIC NEURONS IN ELDERLY PEOPLE, LANCET 1: 668 (1977). / LANCET (1977)
-
WHITEHOUSE, P.J., ALZHEIMER-DISEASE - EVIDENCE FOR SELECTIVE LOSS OF CHOLINERGIC NEURONS IN THE NUCLEUS BASALIS, ANNALS OF NEUROLOGY 10: 122 (1981).
(
10.1002/ana.410100203
) / ANNALS OF NEUROLOGY (1981) -
WINFIELD, D.A., CERTAIN CONNECTIONS OF VISUAL-CORTEX OF MONKEY SHOWN BY USE OF HORSERADISH-PEROXIDASE, BRAIN RESEARCH 92: 456 (1975).
(
10.1016/0006-8993(75)90330-3
) / BRAIN RESEARCH (1975) -
WISNIEWSKI, H.M., AGING OF THE BRAIN AND DEMENTIA, TRENDS IN NEUROSCIENCES 3: 226 (1980).
(
10.1016/0166-2236(80)90085-5
) / TRENDS IN NEUROSCIENCES (1980)
Dates
Type | When |
---|---|
Created | 18 years, 10 months ago (Oct. 5, 2006, 2:30 p.m.) |
Deposited | 1 year, 7 months ago (Jan. 14, 2024, 5:13 p.m.) |
Indexed | 29 minutes ago (Aug. 29, 2025, 6:04 a.m.) |
Issued | 43 years, 5 months ago (March 5, 1982) |
Published | 43 years, 5 months ago (March 5, 1982) |
Published Print | 43 years, 5 months ago (March 5, 1982) |
@article{Whitehouse_1982, title={Alzheimer’s Disease and Senile Dementia: Loss of Neurons in the Basal Forebrain}, volume={215}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.7058341}, DOI={10.1126/science.7058341}, number={4537}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Whitehouse, PJ and Price, DL and Struble, RG and Clark, AW and Coyle, JT and DeLong, Mahlon R.}, year={1982}, month=mar, pages={1237–1239} }