Maternal transmission of Alzheimer's disease: prodromal metabolic phenotype and the search for genes.

Lisa Mosconi, Valentina Berti, Russell H. Swerdlow, Alberto Pupi, Ranjan Duara, Mony de Leon

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

After advanced age, having a parent affected with Alzheimer's disease (AD) is the most significant risk factor for developing AD among cognitively normal (NL) individuals. Although rare genetic mutations have been identified among the early-onset forms of familial AD (EOFAD), the genetics of the more common forms of late-onset AD (LOAD) remain elusive. While some LOAD cases appear to be sporadic in nature, genetically mediated risk is evident from the familial aggregation of many LOAD cases. The patterns of transmission and biological mechanisms through which a family history of LOAD confers risk to the offspring are not known. Brain imaging studies using 2-[ (18) F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG PET) have shown that NL individuals with a maternal history of LOAD, but not with a paternal family history, express a phenotype characterised by a pattern of progressive reductions of brain glucose metabolism, similar to that in AD patients. As maternally inherited AD may be associated with as many as 20 per cent of the total LOAD population, understanding the causes and mechanisms of expression of this form of AD is of great relevance. This paper reviews known genetic mutations implicated in EOFAD and their effects on brain chemistry, structure and function; epidemiology and clinical research findings in LOAD, including in vivo imaging findings showing selective patterns of hypometabolism in maternally inherited AD; possible genetic mechanisms involved in maternal transmission of AD, including chromosome X mutations, mitochondrial DNA and imprinting; and genetic mechanisms involved in other neurological disorders with known or suspected maternal inheritance. The review concludes with a discussion of the potential role of brain imaging for identifying endophenotypes in NL individuals at risk for AD, and for directing investigation of potential susceptibility genes for AD.

Original languageEnglish
Pages (from-to)170-193
Number of pages24
JournalHuman Genomics
Volume4
Issue number3
StatePublished - Feb 1 2010
Externally publishedYes

Fingerprint

Alzheimer Disease
Mothers
Phenotype
Genes
Neuroimaging
Mutation
Brain Chemistry
Endophenotypes
Deoxyglucose
X Chromosome
Nervous System Diseases
Mitochondrial DNA
Positron-Emission Tomography
Epidemiology
Glucose
Brain
Research
Population
Maternal Inheritance

ASJC Scopus subject areas

  • Drug Discovery
  • Genetics
  • Molecular Biology
  • Molecular Medicine

Cite this

Mosconi, L., Berti, V., Swerdlow, R. H., Pupi, A., Duara, R., & de Leon, M. (2010). Maternal transmission of Alzheimer's disease: prodromal metabolic phenotype and the search for genes. Human Genomics, 4(3), 170-193.

Maternal transmission of Alzheimer's disease : prodromal metabolic phenotype and the search for genes. / Mosconi, Lisa; Berti, Valentina; Swerdlow, Russell H.; Pupi, Alberto; Duara, Ranjan; de Leon, Mony.

In: Human Genomics, Vol. 4, No. 3, 01.02.2010, p. 170-193.

Research output: Contribution to journalArticle

Mosconi, L, Berti, V, Swerdlow, RH, Pupi, A, Duara, R & de Leon, M 2010, 'Maternal transmission of Alzheimer's disease: prodromal metabolic phenotype and the search for genes.', Human Genomics, vol. 4, no. 3, pp. 170-193.
Mosconi L, Berti V, Swerdlow RH, Pupi A, Duara R, de Leon M. Maternal transmission of Alzheimer's disease: prodromal metabolic phenotype and the search for genes. Human Genomics. 2010 Feb 1;4(3):170-193.
Mosconi, Lisa ; Berti, Valentina ; Swerdlow, Russell H. ; Pupi, Alberto ; Duara, Ranjan ; de Leon, Mony. / Maternal transmission of Alzheimer's disease : prodromal metabolic phenotype and the search for genes. In: Human Genomics. 2010 ; Vol. 4, No. 3. pp. 170-193.
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